Can the risk of secondary cancer induction after breast conserving therapy be reduced using intraoperative radiotherapy (IORT) with low-energy x-rays?

Abstract

BackgroundRadiation induced secondary cancers are a rare but severe late effect after breast conserving therapy. Intraoperative radiotherapy (IORT) is increasingly used during breast conserving surgery. The purpose of this analysis was to estimate secondary cancer risks after IORT compared to other modalities of breast radiotherapy (APBI - accelerated partial breast irradiation, EBRT - external beam radiotherapy).MethodsComputer-tomography scans of an anthropomorphic phantom were acquired with an INTRABEAM IORT applicator (diameter 4 cm) in the outer quadrant of the breast and transferred via DICOM to the treatment planning system. Ipsilateral breast, contralateral breast, ipsilateral lung, contralateral lung, spine and heart were contoured. An INTRABEAM source (50 kV) was defined with the tip of the drift tube at the center of the spherical applicator. A dose of 20 Gy at 0 mm depth from the applicator surface was prescribed for IORT and 34 Gy (5 days × 2 × 3.4 Gy) at 10 mm depth for APBI. For EBRT a total dose of 50 Gy in 2 Gy fractions was planned using two tangential fields with wedges. The mean and maximal doses, DVHs and volumes receiving more than 0.1 Gy and 4 Gy of organs at risk (OAR) were calculated and compared. The life time risk for secondary cancers was estimated according to NCRP report 116.ResultsIORT delivered the lowest maximal doses to contralateral breast (< 0.3 Gy), ipsilateral (1.8 Gy) and contralateral lung (< 0.3 Gy), heart (1 Gy) and spine (< 0.3 Gy). In comparison, maximal doses for APBI were 2-5 times higher. EBRT delivered a maximal dose of 10.4 Gy to the contralateral breast and 53 Gy to the ipsilateral lung. OAR volumes receiving more than 4 Gy were 0% for IORT, < 2% for APBI and up to 10% for EBRT (ipsilateral lung). The estimated risk for secondary cancer in the respective OAR is considerably lower after IORT and/or APBI as compared to EBRT.ConclusionsThe calculations for maximal doses and volumes of OAR suggest that the risk of secondary cancer induction after IORT is lower than compared to APBI and EBRT.

Utility of CT imaging in a novel form of high‐dose‐rate intraoperative breast radiation therapy

“…This allows for adjustments in applicator placement as well as the collection of information regarding projected dose to adjacent organs and structures, including the skin, chest wall, and heart . HDR is known to increase the risk of secondary malignancies following breast irradiation, including lung, bone, and soft tissue tumours . In addition, radiation exposure has been shown to cause myocardial fibrosis and the potentiation of coronary artery disease .…”

“…In addition, radiation exposure has been shown to cause myocardial fibrosis and the potentiation of coronary artery disease . The maximum radiation doses received by the heart, lungs, and skin are consistently lower for IORT than for external beam whole breast radiation, and thus associated with a lower estimated risk for radiation‐associated damage or oncogenesis . The additional ability for PB‐IORT to allow for alteration of the regular spheroid dose shape to adjust away from the skin and chest wall suggests its capacity to further decrease the radiation dose – and potential deleterious effects – delivered to these structures.…”

“…7 HDR is known to increase the risk of secondary malignancies following breast irradiation, including lung, bone, and soft tissue tumours. 15,16 In addition, radiation exposure has been shown to cause myocardial fibrosis and the potentiation of coronary artery disease. 17 The maximum radiation doses received by the heart, lungs, and skin are consistently lower for IORT than for external beam whole breast radiation, and thus associated with a lower estimated risk for radiation-associated damage or oncogenesis.…”

Risk estimation of second primary cancers after breast radiotherapy

“…The risk of SPC induction was estimated using the NCRP report 116 for treatment plans generated on an anthropomorphic phantom. The study reported a reduced risk estimate associated with IORT and mammosite, compared to EBRT [6].…”

Lifetime cost-effectiveness analysis of intraoperative radiation therapy versus external beam radiation therapy for early stage breast cancer

“…myocardial infarction, coronary revascularization, or death from ischemic heart disease) based on dosage exposure to radiation [ 6 , 7 ]. Additionally, the risk of second solid cancers after radiotherapy for breast cancer is also increased [ 8 , 9 ]. These events not only increase the direct costs in treating these patients over their entire life but as well affect their overall quality of life [ 10 – 15 ].…”