Evaluation of a Novel Field-placement Algorithm for Locoregional Breast Cancer Radiotherapy Including the Internal Mammary Chain.

AIMS: Irradiation of the internal mammary chain (IMC) is increasing following recently published data, but the need for formal delineation of lymph node volumes is slowing implementation in some healthcare settings. A field-placement algorithm for irradiating locoregional lymph nodes including the IMC could reduce the resource impact of introducing irradiation of the IMC. This study describes the development and evaluation of such an algorithm. MATERIALS AND METHODS: An algorithm was developed in which six points representing lymph node clinical target volume borders (based on European Society for Radiotherapy and Oncology consensus nodal contouring guidelines) were placed on computed tomography-defined anatomical landmarks and used to place tangential and nodal fields. Single-centre testing in 20 cases assessed the success of the algorithm in covering planning target volumes (PTVs) and adequately sparing organs at risk. Plans derived using the points algorithm were also compared with plans generated following formal delineation of nodal PTVs, using the Wilcoxon signed rank test. Timing data for point placement were collected. Multicentre testing using the same methods was then carried out to establish whether the technique was transferable to other centres. RESULTS: Single-centre testing showed that 95% of cases met the nodal PTV coverage dose constraints (binomial probability confidence interval 75.1-99.9%) with no statistically significant reduction in mean heart dose or ipsilateral lung V17Gy associated with formal nodal delineation. In multicentre testing, 69% of cases met nodal PTV dose constraints and there was a statistically significant difference in IMC PTV coverage using the points algorithm when compared with formally delineated nodal volumes (P < 0.01). However, there was no difference in axillary level 1-4 PTV coverage (P = 0.11) with all cases meeting target volume constraints. CONCLUSIONS: The optimal strategy for breast and locoregional lymph node radiotherapy is target volume delineation. However, use of this novel points-based field-placement algorithm results in dosimetrically acceptable plans without the need for formal lymph node contouring in a single-centre setting and for the breast and level 1-4 axilla in a multicentre setting. Further quality assurance measures are needed to enable implementation of the algorithm for irradiation of the IMC in a multicentre setting.

Prophylactic amifostine prevents a pathologic vascular response in a murine model of expander-based breast reconstruction.

BACKGROUND: Although expander-based breast reconstruction is the most commonly used method of reconstruction worldwide, it continues to be plagued with complication rates as high as 60% when radiotherapy is implemented. We hypothesized that quantitative measures of radiotherapy-induced vascular injury can be mitigated by utilizing amifostine in a murine model of expander-based breast reconstruction. METHODS: 30 rats were divided into three groups: expander placement (Control), expander placement followed by radiotherapy (XRT), and expander placement followed by radiotherapy with amifostine (AMF/XRT). All groups underwent placement of a sub-latissimus tissue expander. After a 45 day recovery period, all groups underwent vascular perfusion and micro-CT analysis. RESULTS: Micro-CT analysis was used to calculate vessel volume fraction (VVF), vessel number (VN), and vessel separation (VSp). A significant increase in VN was seen in the XRT group as compared to the Control (p = 0.021) and the AMF/XRT (p = 0.027). There was no difference between Control and AMF/XRT (p = 0.862). VVF was significantly higher in XRT than either Control (p = 0.043) and AMF/XRT (p = 0.040), however no difference was seen between Control and AMF/XRT (p = 0.980). VSp of XRT was smaller when compared to both Control and AMF/XRT specimens (p = 0.05 and p = 0.048, respectively), and no difference was seen between Control and AMF/XRT (p = 0.339). CONCLUSIONS: Amifostine administered prior to radiotherapy preserved vascular metrics similar to those of non-radiated specimens. Elevated vascularity demonstrated within the XRT group was not seen in either the Control or AMF/XRT groups. These results indicate that amifostine protects soft tissue in our model from a radiotherapy-induced pathologic vascular response.

Dependence of coronary 3-dimensional dose maps on coronary topologies and beam set in breast radiation therapy: a study based on CT angiographies.

PURPOSE: In left-side breast radiation therapy (RT), doses to the left main (LM) and left anterior descending (LAD) coronary arteries are usually assessed after delineation by prior anatomic knowledge on the treatment planning computed tomography (CT) scan. In this study, dose sensitivity due to interindividual coronary topology variation was assessed, and hot spots were located. METHODS AND MATERIALS: Twenty-two detailed heart models, created from heart computed tomography angiographies, were fitted into a single representative female thorax. Two breast RT protocols were then simulated into a treatment planning system: the first protocol comprised tangential and tumoral bed beams (TGs_TB) at 50 + 16 Gy, the second protocol added internal mammary chain beams at 50 Gy to TGs_TB (TGs_TB_IMC). For the heart, the LAD, and the LM, several dose indicators were calculated: dose-volume histograms, mean dose (Dmean), minimal dose received by the most irradiated 2% of the volume (D2%), and 3-dimensional (3D) dose maps. Variations of these indicators with anatomies were studied. RESULTS: For the LM, the intermodel dispersion of Dmean and D2% was 10% and 11%, respectively, with TGs_TB and 40% and 80%, respectively, with TGs_TB_IMC. For the LAD, these dispersions were 19% (Dmean) and 49% (D2%) with TGs_TB and 35% (Dmean) and 76% (D2%) with TGs_TB_IMC. The 3D dose maps revealed that the internal mammary chain beams induced hot spots between 20 and 30 Gy on the LM and the proximal LAD for some coronary topologies. Without IMC beams, hot spots between 5 and 26 Gy are located on the middle and distal LAD. CONCLUSIONS: Coronary dose distributions with hot spot location and dose level can change significantly depending on coronary topology, as highlighted by 3D coronary dose maps. In clinical practice, coronary imaging may be required for a relevant coronary dose assessment, especially in cases of internal mammary chain irradiation.

Comparison of thermal damage of the internal thoracic artery using ultra high radiofrequency and monopolar diathermy.

BACKGROUND: The internal thoracic artery (ITA) has been accepted worldwide as a first choice conduit for myocardial revascularisation. It still remains questionable what is the best method for ITA harvesting in a skeletonized fashion according to structural integrity of artery, as a risk factor of early and late graft failure. The purpose of this study was to determine the impact of the ultra-high radiofrequency energy used for ITA harvesting on arterial structural integrity, in particular on the endothelial layer. METHODS: Seventy-four ITA specimens were divided into two groups depending on device used for harvesting (radiofrequency-knife (RF) or electrocauter (EC)). Thermal damage on arterial structural integrity was measured using light microscope, morphometric imaging analysis and immunohistochemical methods. RESULTS: Thermal damage of endothelium was 2.8 times higher in EC than in RF group (p = 0.041) and 5 times higher in patients older than 66 years of age (p = 0.002). Extent of endothelial damage (graded from 0 to 3) was significantly higher in EC group (p = 0.03). Also, in EC group, in patients older than 66 years of age higher proportion of extent of endothelial damage was found (p = 0.027). CONCLUSIONS: The endothelial damage was more often in EC than in RF group as in the patients older than 66 years of age. Demonstrated results suggest that the radiosurgery in comparison to conventional electrocautery is safe and effective method, and significantly reduces thermal damage to endothelial layer of artery.

Is there an indication for digital subtraction angiography in the assessment of irradiation-induced vascular damage before free flap surgery by the means of the internal mammary vessels?

Secondary breast reconstruction is increasingly performed after postmastectomy radiotherapy. Damage to blood vessel walls is one of the adverse effects of irradiation therapy, which may jeopardize reconstructive free flap surgery. It would be of great importance to be informed about the quality of the recipient vessel before reconstructive surgery. The aim of this study was to prospectively assess the value of preoperative angiography in the assessment of radiation-induced arterial damage and to relate the findings to the degree of vascular damage found during the operation and with histology. This study included women who had been treated with thoracic radiotherapy and required free flap breast reconstruction. Preoperative angiographic, intraoperative quality and histological findings of vessels were scored and compared together with the occurrence of postoperative complications. In 34 patients a total of 40 free flaps breast reconstruction were performed. Total 21 internal mammary arteries had been within the field of irradiation. In only two out of six patients with aberrant angiographies the internal mammary artery has been within the field of irradiation. This study concludes that damage to the internal mammary vessels cannot always be detected preoperatively by angiography, or even by intraoperative examination.

Low-level-laser irradiation induces photorelaxation in coronary arteries and overcomes vasospasm of internal thoracic arteries.

BACKGROUND AND OBJECTIVE: As low-level laser irradiation (LLLI) seems to induce vasodilation besides many other known biological effects, LLLI has been increasingly used in therapy of medical conditions with various irradiation parameters. The aim of this study was to investigate the effect of LLLI on photorelaxation of human coronary and internal thoracic arteries (ITA). MATERIALS AND METHODS: Thirty vessel segments of ITA used for routine coronary artery bypass grafting as well as left anterior descending coronary arteries (LAD) of patients undergoing cardiac transplantation were cut into 4-mm rings stored in a modified Krebs-Henseleit solution and evaluated in a myograph. Both types of vessel segments were irradiated by a semiconductor non-thermal GaAs diode laser operating at a wavelength of 680 nm. After precontraction with thromboxane agonist U44619, respective relaxation responses were evaluated and compared to pharmacological dilatation induced by substance P. RESULTS: Mean pharmacological vasodilation by substance P was 22.6 ± 3.3%, 12.8 ± 1.4%, and 20.4 ± 3.2% in macroscopic healthy LAD, LAD with atheromatous plaque, and ITA, respectively. Average photorelaxation induced by LLLI was 16.5 ± 2.0%, 1.9 ± 1.7%, and 6.8 ± 4.7%, accordingly. Vasodilatatory responses induced either by substance P or administration of LLLI were significantly decreased in LAD with atheromatous plaque (P < 0.0001). Vasospasms of ITA segments occurring during experiments could be abandoned when LLLI was administered. CONCLUSION: Macroscopic healthy LAD exposed to LLLI revealed significant photorelaxation. With the administration of LLLI, 73% of the maximal obtainable effect by an endothelium-dependent vasodilator could be reached. Furthermore, LLLI has the potential to overcome vasospasms of ITA.

Conduit choice for coronary artery bypass grafting after mediastinal radiation.

OBJECTIVE: Patients who have undergone prior mediastinal radiation might require coronary artery bypass grafting. However, there is some concern regarding potential radiation damage to the internal thoracic artery. Our objective was to assess the late patency of the internal thoracic artery and venous grafts in patients with prior mediastinal radiation. METHODS: Patients undergoing coronary artery bypass grafting at our clinic after prior mediastinal radiation were identified, and medical records, including operative reports, clinical notes, and coronary angiography, were reviewed. RESULTS: Between 1985 and 2005, 138 patients had coronary artery bypass grafting after mediastinal radiation. Of these, 25 underwent clinically indicated postoperative angiography. The mean patient age was 56.1 +/- 13.8 years, and 24% were female. All patients received between 3000 and 6000 rads in fractionated doses. Seventy-two percent of patients had 3-vessel coronary artery disease. At late angiography (mean, 2.2 years), 6 (32%) of 19 internal thoracic arteries and 13 (27%) of 48 venous or radial arterial conduits showed stenosis of 70% or greater (P = .72). Assessing only grafts that were anastomosed to the left anterior descending coronary artery, 35% (6 of 17) of internal thoracic artery grafts and 60% (3 of 5) of non-internal thoracic artery grafts showed narrowing of 70% or greater (P = .61). Among patients who received a graft to the left anterior descending coronary artery (n = 113), however, age-adjusted survival at 5 years was superior among those receiving an internal thoracic artery graft to the left anterior descending coronary artery. CONCLUSIONS: Internal thoracic artery graft patency among patients with prior radiation was less than expected and similar to that for venous grafts, although the effect of conduit disease versus distal target vessel runoff is unknown. Despite this, late survival was superior among those receiving an internal thoracic artery graft to the left anterior descending coronary artery. These data support use of an internal thoracic artery graft to the left anterior descending coronary artery when it appears grossly to be an acceptable conduit.

Thoracic radiation therapy and suitability of internal thoracic arteries for myocardial revascularization.

INTRODUCTION AND BACKGROUND: Myocardial revascularization using internal thoracic arteries (ITAs) has been associated with superior clinical outcome. This study addresses the question of whether internal mammary arteries are unsuitable for grafting due to radiation-based damage in patients with history of thoracic radiation therapy. We review our experience in this subset of surgical candidates. PATIENTS AND METHODS: Forty-nine patients undergoing elective coronary artery bypass grafting with use of at least one ITA were enrolled and matched to 49 comparable nonirradiated individuals by propensity scoring system. Preoperative and postoperative data were collected and compared. A 18-month clinical follow-up was performed. RESULTS: Intraoperative mammary artery flow was assessed by transthoracic Doppler echocardiography probe, and there was no significant difference between irradiated and nonirradiated individuals (36 +/- 8.3 mL/min vs 39 +/- 7.2 mL/min, p = 0.15). The two study groups were also comparable in terms of survival (overall mortality, 2%) and recurrence of angina and perfusion defect at control stress perfusion nuclear scan (p = 0.99 and p = 0.77, respectively). One arterial graft showed stenosis at postoperative angiography. The dose of radiation therapy administered did not correlate with graft flow values after anastomosis. CONCLUSION: Our data suggest that the use of a monolateral or bilateral ITA is not associated with early graft failure in patients with history of chest/mediastinal irradiation. Skeletonization harvesting technique might be recommended because of the frequent presence of fibrous tissue around the in situ vessel. Arterial graft stenosis in thorax-irradiated patients should be attributed to the primary atherosclerotic disease rather than to irradiation itself.

Choice of recipient vessels in delayed TRAM flap breast reconstruction after radiotherapy.

This study compared the use of the internal mammary and thoracodorsal recipient vessels in a uniform group of patients who underwent delayed TRAM flap reconstruction after radiotherapy, focusing on usability rates and outcomes. The authors identified 123 delayed TRAM flap patients who had undergone postmastectomy radiotherapy from a prospective database (1990 to 2001). Recipient vessel unusability rates were calculated on the basis of reports of inspection of a vessel, either by direct intraoperative dissection or by findings from color Doppler examination (internal mammary vessels only). Charts were reviewed for outcomes including flap loss, vascular complications, fat necrosis, and lymphedema; t-test and chi-square analyses were performed to compare outcomes and unusability rates, and multiple regression analysis was performed to determine factors influencing outcome. Of the 123 planned free TRAM flaps, 106 were completed as free flaps and 17 were performed as pedicled flaps because of unusable recipient vessels. Of the free flaps, 45 were anastomosed to the internal mammary vessels, 55 to the thoracodorsal vessels, and six to other vessels. The internal mammary and thoracodorsal groups did not differ significantly in body mass index, abdominal scars, smoking history, time delay between irradiation and TRAM flap reconstruction, or flap ischemia time. Radiation doses to the axilla (thoracodorsal), internal mammary chain, and supraclavicular fossa were similar between the groups. The internal mammary vessels were rejected in 11 (20 percent) of 56 cases, and the thoracodorsal vessels were rejected in 19 (26 percent) of 74 cases (p = 0.42). In cases with unusable internal mammary vessels, 46 percent (n = 5) had inadequate veins, 27 percent (n = 3) had inadequate arteries, and in 27 percent (n = 3) both vessels were inadequate. In the 19 cases with unusable thoracodorsal vessels, 84 percent (n = 16) were excessively scarred, 11 percent (n = 2) had inadequate vessels, and 5 percent (n = 1) were absent. Outcomes were similar regardless of recipient vessels used (internal mammary versus thoracodorsal): total flap loss, 0 percent versus 4 percent (p = 0.20); vascular complications, 6.7 percent versus 11 percent (p = 0.46); arm lymphedema, 4.4 percent versus 9 percent (p = 0.37); partial flap loss, 9 percent versus 6 percent (p = 0.54); and fat necrosis, 18 percent versus 15 percent (p = 0.69). Multivariate analysis revealed a trend for higher complication rates in smokers and with the use of the thoracodorsal vessels as the recipients. Overall, no discernible unusability or outcome differences were detected between the internal mammary and thoracodorsal groups.

The long-term effects of internal mammary chain irradiation and its role in the vascular supply of the pedicled transverse rectus abdominis musculocutaneous flap breast reconstruction.

With an increase in breast-sparing surgery and adjuvant radiotherapy, there has been a concomitant increase in the complexity of breast reconstruction. The effects of radiotherapy on the internal mammary artery were evaluated with respect to flap viability for conventional transverse rectus abdominis musculocutaneous breast reconstruction using the irradiated rectus muscle. Twenty-eight women who received postoperative irradiation for breast cancer were studied. All women had unilateral irradiation, and evaluation of the internal mammary arteries was performed at least 1 year after the completion of radiotherapy to allow for fibrosis and long-term vascular changes. Examination of the internal mammary artery (upper and lower chains) was performed using color Doppler sonography to assess vessel diameter, peak systolic velocity, and blood flow. The nonirradiated side was compared to the radiated internal mammary artery as an internal control. Based on the details of prior radiotherapy, the 28 women were designated into two groups. Group I included 14 women with radiation portals that specifically treated the internal mammary chain; the average dose to the internal mammary chain was 47.44 Gy. Group II comprised 14 patients that received tangential portals that did not directly target the internal mammary chain region; the average radiation dose was 48.21 Gy to the chest wall. No statistical difference was observed in group I between the irradiated and nonirradiated side for vessel diameter (p = .8631) or peak systolic velocity (p = .2646). However, an increase in blood flow on the irradiated side was significant (p = .0321).(ABSTRACT TRUNCATED AT 250 WORDS)

Left internal thoracic artery graft occlusion following mediastinal radiation therapy.

Premature coronary artery disease is a late consequence of mediastinal radiation therapy. Many of these patients have been successfully treated with coronary bypass surgery. A 51-year-old man underwent bypass surgery for severe multivessel coronary disease 18 years following radiation therapy for a posterior mediastinal tumor. Recurrent angina 1 year later occurred following closure of the left internal thoracic artery graft. We suspect that this occurred as a consequence of injury sustained during mediastinal irradiation. Patients who have undergone prior mediastinal radiation therapy may not be assured the excellent long-term patency of the internal thoracic artery graft which has been reported for the general population. Saphenous vein grafts probably should be considered instead.