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BACKGROUND: Clinical guidelines for internal mammary chain (IMC) irradiation are not uniformly accepted, with notable differences between countries. This survey examines IMC irradiation practices among radiation oncologists in Italy and Spain. MATERIALS AND METHODS: An online survey was distributed to radiation oncologists via Google Forms. It included 26 questions, 9 on participants' epidemiological data and 17 on IMC irradiation. Participation was voluntary with no financial incentives. RESULTS: The survey, conducted in March and April 2024, received 94 responses (51 from Italy, 43 from Spain). Spanish oncologists are more likely to include IMC irradiation with any axillary involvement, regardless of tumor size or location. Italian oncologists more often take definitive stances of "always" or "never," while Spanish oncologists prefer the "sometimes" option. No significant differences were found in IMC definition, technique, doses, or respiratory control. CONCLUSIONS: IMC radiotherapy indications remain controversial, with differences between Italian and Spanish oncologists.

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Objetivo: Evaluar la tasa de detección y la implicación terapéutica de la infiltración de la cadena mamaria interna (ICMI) mediante tomografía por emisión de positrones (PET) y resonancia magnética (RM) con 18F-fluorodesoxiglucosa (18F-PET/RM) en la estadificación de pacientes con cáncer de mama. Método: Estudio prospectivo, 41 mujeres con cáncer de mama (estadio ≥ IIB) estadificadas mediante 18F-FDG-PET/RM. Estudio en dos fases: imágenes mamarias (decúbito prono), cuerpo completo (supino). Estadificación TNM por consenso entre especialista en Medicina Nuclear y Radiología. Estudio vaso aferente (VA) a cadena mamaria interna (CMI) por RM mamaria. Correlación ICMI con edad, VA-CMI, estadificación T, cuadrante, infiltración axilar y a distancia. Revaloración terapéutica en comité multidisciplinar. Resultados: Tasa de detección de ICMN de 34% (14/41), siendo 8/14 < 55 años. Todas las 14 pacientes con ICMI muestran VA-CMI, en seis de ellas (43,9%) sin VA-axilar. De 27/41 sin ICMI, en 13 (48,1%) solo VA-axilar, en los 14 restantes (51,9%) VA-axilar y VA-CMI. Un total de 57% (8/14) son multicéntricos y 42% (6/14) focales, en cuadrantes internos en 4/6 (66,7%). En 1/14 (7,1%) solo ICMI, en 9/14 (64,3%) axilar y CMI y en 4/14 (28,6%) lesiones a distancia. Decisión del comité: sin tratamiento adicional en 27/41 (65,8%), radioterapia torácica en 10/41 (24,4%) y terapia sistémica en 4/41 (9,7%). Conclusión: La tasa de detección de la ICMI en la estadificación del cáncer de mama mediante 18F-FDG PET/RM es de 34%. Son factores asociados la edad, los tumores multicéntricos, los de cuadrantes internos, la existencia de VA-CMI, la estadificación NM. La evidencia de ICMI permite la individualización de la terapia, indicando la radioterapia torácica en 24,4%.(AU)

Objective: To evaluate the detection rate and therapeutic implication of the infiltration of the internal mammary chain (IMCI) by [18F]FDG PET/MRI for staging of patients with breast cancer. Methods: Prospective study including 41 women with breast cancer (stage ≥IIB) staged by [18F]FDG PET/MR. Two-phase exam: breast imaging (prone), whole-body (supine). TNM stage assessed by peer consensus with Nuclear Medicine and Radiology specialists. Study of the afferent vessel (AV) to IMC by breast MRI. IMCI was correlated with age, AV-IMC, T stage, breast quadrants, axillary and distant infiltration. Therapeutic re-evaluation by a multidisciplinary committee. Results: IMCI detection rate of 34% (14/41), with 8/14 patients under 55 years of age. All 14 patients with IMCI showed AV-IMC, 6 of them (43.9%) without VA-axillary. Of 27/41 patients without IMCI, in 13 (48.1%) only AV-axillary was found, in the remaining 14 (51.9%), AV-axillary and AV-IMC was found. In 57% (8/14) tumours were multicentric and 42% (6/14) focal, in inner quadrants in 4/6 (66.7%). In 1/14 patient (7.1%) only IMCI was found, in 9/14 (64.3%) axillary and IMC, in 4/14 patients (28.6%) distant lesions were detected. Committee re-evaluation: no further treatment in 27/41 patients (65.8%), thoracic radiotherapy in 10/41 patients (24.4%), systemic therapy in 4/41 patients (9.7%). Conclusion: Our detection rate of IMCI in breast cancer staging by [18F]FDG PET/MR was 34%. Related factors were age, multicentric tumours, inner quadrants, detection of AV-IMC, NM staging.The evidence of IMCI allowed tailored therapy, with thoracic radiotherapy implementation in 24.4% of patients.(AU)

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OBJECTIVE: To evaluate the detection rate and therapeutic implication of the infiltration of the internal mammary chain (IMCI) by [18F]FDG PET/MRI for staging of patients with breast cancer. METHODS: Prospective study including 41 women with breast cancer (stage ≥ IIB) staged by [18F]FDG PET/MR. Two-phase exam: breast imaging (prone), whole-body (supine). TNM stage assessed by peer consensus with Nuclear Medicine and Radiology specialists. Study of the afferent vessel (AV) to IMC by breast MRI. IMCI was correlated with age, AV-IMC, T stage, breast quadrants, axillary and distant infiltration. Therapeutic re-evaluation by a multidisciplinary committee. RESULTS: IMCI detection rate of 34% (14/41), with 8/14 patients under 55 years of age. All 14 patients with IMCI showed AV-IMC, 6 of them (43.9%) without VA-axillary. Of 27/41 patients without IMCI, in 13 (48.1%) only AV-axillary was found, in the remaining 14 (51.9%), AV-axillary and AV-IMC was found. In 57% (8/14) tumours were multicentric and 42% (6/14) focal, in inner quadrants in 4/6 (66.7%). In 1/14 patient (7.1%) only IMCI was found, in 9/14 (64.3%) axillary and IMC, in 4/14 patients (28.6%) distant lesions were detected. Committee re-evaluation: no further treatment in 27/41 patients (65.8%), thoracic radiotherapy in 10/41 patients (24.4%), systemic therapy in 4/41 patients (9.7%). CONCLUSION: Our detection rate of IMCI in breast cancer staging by [18F]FDG PET/MR was 34%. Related factors were age, multicentric tumours, inner quadrants, detection of AV-IMC, NM staging. The evidence of IMCI allowed tailored therapy, with thoracic radiotherapy implementation in 24.4% of patients.

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BACKGROUND: Fatigue is a common and disabling symptom after breast cancer (BC) treatment, significantly impacting patients' quality of life. We aimed to assess the impact of radiation therapy (RT) modalities on fatigue one year after treatment among patients with early-stage BC. METHODS: We used CANTO-RT, a subcohort of CANcer TOxicity (CANTO; NCT01993498), a multicentric nationwide prospective cohort of stages I-III BC treated from 2012 to 2017. Our primary outcome was severe global fatigue 1 year after RT completion (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 score ≥40/100). The secondary outcomes included severe physical, emotional and cognitive fatigue (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-FA12). RT-related variables were used as independent variables. Multivariable logistic regression models assessed associations between RT-related variables and fatigue. RESULTS: The final analytic cohort included 3295 patients. The prevalence of severe global fatigue 1 year after treatment was 33.3%. Internal mammary chain RT (adjusted odds ratio [OR] 1.48 [95% confidence interval [CI] 1.03-2.13; p = 0.0355]) and normofractionated RT (adjusted OR 1.88 [95% CI 1.06-3.31; p = 0.0298]) were associated with increased odds of severe global fatigue. In addition, there was a significant association between normofractionated RT (adjusted OR 1.849 [95% CI 1.04-3.3; p = 0.0354]) and an increased likelihood of severe physical fatigue. CONCLUSION: We found a significant association between internal mammary chain RT (versus No), normofractionated RT (versus hypofractionated RT) and increased likelihood of persistent severe global fatigue. Our data add to the current understanding of treatment-related factors affecting fatigue after BC and could lead to personalised interventions to improve the prevention and management of this disabling symptom.

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AIMS: The 15-year results of the EORTC 229922-10925 phase III trial showed a significant reduction in breast cancer mortality and breast cancer recurrences after internal mammary chain (IMC) and medio-supraclavicular irradiation. Unexpectedly, cardiac death was not increased, and the incidence of cardiac events did not differ between left- and right-sided cases, although target volume coverages and organ at risk doses were unknown. Therefore, a planning study was carried out comparing the past and the present, to eventually enable, thereafter, an increased therapeutic ratio of IMC irradiation. MATERIALS AND METHODS: A planning study was carried out on target volume coverage and organ at risk doses for whole-breast irradiation (WBI) ± IMC comparing the results between two-dimensional radiotherapy (free-breathing), hybrid intensity-modulated radiotherapy (IMRT; breath-hold) and robust intensity-modulated proton therapy (IMPT; free-breathing) for 10 left-sided breast cancer cases. Two-dimensional radiotherapy consisted of two tangential wedged photon breast fields and mixed electron/photon beams for the IMC. Hybrid IMRT included two tangential photon breast fields (70%) complemented with IMRT (30%). IMPT plans were created using multi-field robust optimisation (5 mm set-up and 3% range uncertainties) with two (WBI) or three (WBI + IMC) beams. RESULTS: Target volume dose objectives were met for hybrid IMRT and IMPT. For two-dimensional radiotherapy, target coverage was 97% and 83% for breast and IMC, respectively. The mean heart dose for WBI only was <2 Gy for all techniques. For WBI + IMC, heart doses (mean heart dose, mean left anterior descending region, volume of the heart receiving 5 Gy (V5) were significantly higher for two-dimensional radiotherapy when compared with contemporary techniques. The V5 left anterior descending region reduced from 100% (two-dimensional radiotherapy) to 70% and 20% for hybrid IMRT and IMPT, respectively. CONCLUSION: Contemporary radiotherapy techniques result in improved target volume coverage and significantly decreased heart doses for WBI + IMC radiotherapy. Hence, nowadays an increased therapeutic ratio of elective IMC irradiation may be anticipated.

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BACKGROUND: In the multimodal breast-conserving curative therapy of some high-risk breast cancer patients, extended external beam radiotherapy (EBRT) not only to the breast but also to the supraclavicular fossa and the internal mammary chain (parasternal region (PSR)) is indicated. We report a dosimetric study on the EBRT of the breast ("B") and the breast including PSR ("B + PSR"), comparing the supine and the laterally tilted prone patient positions in free breathing. METHODS: The planning CT scans of 20 left- and 20 right-sided patients were analyzed. EBRT plans were calculated with 3D conformal EBRT (3D) and with intensity-modulated EBRT (IMRT) for "B" and "B + PSR" in the prone and supine positions. The mean and threshold doses were computed. The quality of EBRT plans was compared with an overall plan assessment factor (OPAF), comprising three subfactors, homogeneity, conformity, and radiogenic exposure of OAR. RESULTS: In the EBRT of "B", prone positioning significantly reduced the exposure of the OARs "heart" and "ipsilateral lung" and "lymphatic regions". The OPAF was significantly better in the prone position, regardless of the planning technique or the treated breast side. In the EBRT of "B + PSR", supine positioning significantly reduced the OAR "heart" exposure but increased the dose to the OARs "ipsilateral lung" and "lymphatic regions". There were no significant differences for the OPAF, independent of the irradiated breast side. Only the IMRT planning technique increased the chance of a comparatively good EBRT plan. CONCLUSION: Free breathing prone positioning significantly improves plan quality in the EBRT of the breast but not in the EBRT of the breast + PSR.

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Background and Purpose: The low rate of internal mammary node (IMN) recurrence was attributed to systemic therapy and internal mammary chain (IMC) coverage by the tangential fields of irradiation. This study aimed to evaluate the incidental irradiation dose to the IMC in breast cancer patients after surgery and to estimate the clinical predictive parameters affecting the magnitude of the IMC. Materials and Methods: A total of 138 patients treated with postmastectomy radiotherapy and 210 patients undergoing radiotherapy after breast-conserving surgery (BCS) in our hospital were retrospectively analyzed. The mean dose (Dmean) to the IMC and the first to third intercostal spaces of IMC levels (ICS1-3) were evaluated. We evaluated the IMC coverage according to the type of surgery and whether the ipsilateral supraclavicular fossa (SCF) was included in the irradiation field. Results: The incidental radiation dose to the IMC was 29.69 Gy, and the dose delivered to the IMC, ICS1, and ICS2 showed a greater coverage in the modified radical mastectomy (MRM) group when compared with the BCS group (32.85 vs. 27.1 Gy, 26.6 vs. 12.5 Gy, 34.63 vs. 30.42 Gy). The dose delivered to ICS3 showed no difference between the MRM and BCS groups (37.41 vs. 36.24 Gy). Furthermore, 131 patients (37.64%) received radiotherapy to the chest wall and ipsilateral SCF. In the univariate analysis, both surgery type and SCF irradiation were parameters affecting the Dmean of incidental radiation to the IMC (r = -0.179, P = 0.001; r = -0.175, P = 0.001). In the multivariate analysis, surgery type was the only correlative factor that affected incidental radiation dose to the IMC (r = -3.534, P = 0.000). Conclusion: The real influencing factor of incidental dose to the IMC was the surgery form rather than the accession of SCF irradiation.

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INTRODUCTION: The aim of the present study was to estimate the impact of the addition of internal mammary chain (IMC) irradiation in node-positive left-sided breast cancer (BC) patients undergoing regional nodal irradiation (RNI) and comparatively evaluate excess relative and absolute risks of radiation-induced lung cancer/BC and ischaemic heart disease for intensity-modulated radiotherapy (IMRT) versus 3D conformal radiotherapy (3D-CRT). METHODS: Four treatment plans were created (3D-CRT and IMRT -/+ IMC) for each of the 10 evaluated patients, and estimates of excess relative risk (ERR) and 10-year excess absolute risk (EAR) were calculated for radiation-induced lung cancer/BC and coronary events using linear, linear-exponential and plateau models. RESULTS: The addition of IMC irradiation to RNI significantly increased the dose exposure of the heart, lung and contralateral breast using both techniques, increasing ERR for secondary lung cancer (58 vs. 44%, p = 0.002), contralateral BC (49 vs. 31%, p = 0.002) and ischaemic heart disease (41 vs. 27%, p = 0.002, IMRT plans). IMRT significantly reduced the mean cardiac dose and mean lung dose as compared to 3D-CRT, decreasing ERR for major coronary events (64% 3D-CRT vs. 41% IMRT, p = 0.002) and ERR for secondary lung cancer (75 vs. 58%, p = 0.004) in IMC irradiation, without a significant impact on secondary contralateral BC risks. CONCLUSION: Although IMC irradiation has been shown to increase survival rates in node-positive BC patients, it increased dose exposure of organs at risk in left-sided BC, resulting in significantly increased risks for secondary lung cancer/contralateral BC and ischaemic heart disease. In this setting, the adoption of IMRT seems advantageous when compared to 3D-CRT.

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BACKGROUND: Whether to prophylactically irradiate the ipsilateral internal mammary chain (IMC) in post-mastectomy radiotherapy (PMRT) remains controversial because of equivocal clinical benefits against the added toxicities. Our previous study revealed that the cardiac dose was decreased during left-sided breast radiotherapy with abdominal deep inspiration breath-hold (aDIBH) as compared with free-breathing (FB) and thoracic deep inspiration breath-hold (tDIBH). Here we present the dosimetric advantage of aDIBH for patients undergoing PMRT with IMC coverage. METHODS: We prospectively analyzed 19 patients with left-sided breast cancer who underwent PMRT. Patients underwent computed tomography (CT) simulation under both free-breathing (FB) and aDIBH. The heart, left anterior descending coronary artery (LAD), lungs, and the contralateral breast was defined as organs at risk (OARs). Three-dimensional conformal radiation therapy (3D-CRT), inverse planning intensity-modulated radiation therapy (IMRT), and volumetric modulated arc therapy (VMAT) were used to calculate the doses received by both the planning target volume (PTV) and OARs, which were compared using the Wilcoxon signed-rank test. RESULTS: Compared with FB, the Dmean of the heart and LAD were respectively reduced by 3.5 Gy (P<0.003) and 8.9 Gy (P<0.001) in 3D-CRT, 2.6 Gy (P<0.001), and 7.8 Gy (P=0.001) in IMRT, 1.5 Gy (P<0.001) and 4.5 Gy (P=0.001) in VMAT plans under aDIBH. Among all these plans, the Dmean of the heart was lowest in aDIBH IMRT and 1.3 Gy lower than in aDIBH VMAT (P=0.002). aDIBH IMRT also resulted in a significantly reduced dose to the ipsilateral lung than plans under FB (P<0.05). Dmean and V5 to the contralateral lung and breast were higher in VMAT plans (P<0.05). CONCLUSIONS: Using an immobilization-assisted aDIBH technique, radiation doses to the heart can be kept at reasonably low levels even if IMC is included in the clinical target volume (CTV). Among 3D-CRT, IMRT, and VMAT plans, IMRT plus aDIBH results in the best heart-sparing effect. We recommend that the aDIBH technique be routinely applied in suitable patients if the IMC is irradiated.

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BACKGROUND: Deep-inspiration breath-hold (DIBH) reduces radiation dose to the heart in patients undergoing locoregional breast radiotherapy. In the context of tangential irradiation of the breast/ chest wall, a voluntary breath hold (vDIBH) technique has been shown to be as reproducible as a machine-assisted breath hold technique using the active breathing co-ordinator (ABC™, Elekta, Crawley, UK, ABC_DIBH). This study compares set-up reproducibility for vDIBH versus ABC_DIBH in patients undergoing volumetric-modulated arc radiotherapy (VMAT) for breast cancer, both with and without wax bolus. METHOD: Patients with breast cancer requiring pan regional lymph node VMAT +/- wax bolus in breath-hold were CT scanned in vDIBH and ABC_DIBH. Patients were randomised to receive one technique for fractions 1-7 and the other for fractions 8-15. Daily cone beam computed tomography (CBCT) was performed and registered to planning-CT using bony anatomy. Within-patient comparisons of mean daily chest wall position were made using a paired t-test. Population, systematic (∑) and random errors (α) were estimated. Intrafraction reproducibility was assessed by comparing chest wall position and diaphragm movement between consecutive breath holds on CBCT. RESULTS: 16 patients were recruited. All completed treatment with both techniques (9 patients with wax bolus, 7 patients without). CBCT derived ∑ were 2.1-6.4 mm (ABC_DIBH) and 2.1-4.9 mm (vDIBH), α were 1.7-2.6 mm (ABC_DIBH) and 2.2-2.7 mm (vDIBH) and mean daily chest wall displacements (MD) were 0.0-1.5 mm (ABC_DIBH) and -0.1-1.6 vDIBH (all p non-significant). Chest wall and diaphragm position was equivalent between consecutive breath holds in ABC and vDIBH (median difference 1.0 mm and 0.8 mm respectively, non p significant) demonstrating equivalent intrafraction reproducibility. CONCLUSION: This study demonstrates that a simple voluntary breath hold technique is feasible in combination with VMAT (+/- bolus) and is as reproducible as ABC_DIBH with VMAT for the irradiation of the breast and axillary and IMC lymph nodes in breast cancer patients.

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INTRODUCTION: The risk of radiotherapy-associated cardiovascular disease has been a concern for decades in breast cancer survivors. The objective of our study is to evaluate the dosimetric benefit of Deep Inspiratory Breath-hold technique (DIBH) on organs-at-risk (OAR) sparing in left-sided breast cancer radiotherapy and to find out pre-treatment predictors of cardiac doses for guiding patient selection for DIBH. MATERIAL AND METHODS: Pre-radiotherapy planning CT scans were done in Free Breathing (FB) and in DIBH [using Active Breathing Coordinator system (ABC™)] in 31 left sided breast cancer patients. 3DCRT plans were generated for both scans. Comparison of anatomical and dosimetric variables were done using paired t test and correlation was evaluated using Pearson correlation. Linear regression was used to get independent predictors of cardiac sparing and Receiver Operating Characteristic (ROC) curve analysis was done to find out the specific threshold of the predictors. RESULTS: There was a 39.15% reduction in mean heart dose in DIBH compared to FB (2.4 Gy vs 4.01 Gy) (p < 0.001), 19% reduction in maximum Left Anterior Descending (LAD) dose and a 9.9% reduction in ipsilateral lung mean dose (p = 0.036) with DIBH. A significant correlation was observed between reduction in Heart Volume in Field (HVIF) and Maximum Heart Depth (MHD) with reduction in mean heart dose. Reduction in HVIF (ΔHVIF) independently predicted cardiac sparing. CONCLUSION: DIBH leads to significant reduction in OAR doses and is suggested for all patients of left-sided breast cancer undergoing radiotherapy. However, HVIF and MHD predicted for cardiac sparing and threshold criteria of ΔHVIF and ΔMHD may be used by centres with high workload to select patients for DIBH.

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Objective:To investigate the dosimetric characteristics, acute toxicity and short-term efficacy of postmastectomy hypofractionated internal mammary (IM) chain irradiation with electrons in patients with high-risk breast cancer.Methods:A total of 155 patients with breast cancer who underwent modified mastectomy between November 2018 and January 2020 were selected. Among them, 137(88.4%) patients were classified as stage Ⅲ and 18(11.6%) as stage Ⅱ. All patients received standard chemotherapy, endocrine therapy and anti-Her2 targeted therapy. CTV im was divided into three subregions: CTV im1, CTV im2 and CTV im3, which represented the first, second and third intercostal IM, respectively. The planning target volume of subraclavicular region (PTV sc) was delineated. CTV cw and CTV im were irradiated with 6-15 MeV electron at 43.5 Gy in 15 fractions over 3 weeks. Moreover, PTV sc was irradiated with 6 MV X-ray at 43.5 Gy in 15 fractions over 3 weeks using two-dimensional radiotherapy (2DRT) or three-dimensional radiotherapy (3DRT). The dosimetric characteristics of CTV im, PTV sc, lung, heart, left anterior descending coronary artery (LAD) and right coronary artery (RA) were evaluated, and the acute toxicity and short-term efficacy were analyzed. Results:The mean dose (D mean) of CTV im was (43.3±2.6) Gy, D 95% was (30.5±8.3) Gy, V 90% was (85.0±10.5)% and V 80% was (91.0±7.4)%, respectively. The corresponding parameters of CTV im1 were significantly lower than those of CTV im2 and CTV im3(all P<0.001). Body mass index exerted no significant effect on IM dose ( P>0.05). Compared with 2DRT, 3DRT for SC significantly increased theD mean of CTV im[(43.4±2.6) Gy vs.(41.4±2.3) Gy, P=0.021], and the hot spot within PTV sc[V 110%: (26.7±17.5) cm 3vs.(12.5±8.4) cm 3, P=0.018; V 120%: (6.1±5.3) cm 3vs.(2.0±2.6) cm 3, P=0.023]. TheD mean of the ipsilateral lung was (9.8±1.9) Gy, and V 20Gy was (19.7±4.7)%. TheD mean of heart was (3.3±1.7) Gy in the whole group, (4.7±1.4) Gy for the left-sided breast cancer and (2.6±1.2) Gy for the right-sided breast cancer, respectively. TheD mean of LAD for the left-sided breast cancer was (13.9±4.9) Gy. TheD mean of RA for the right-sided breast cancer was (7.5±3.7) Gy. The incidence rates of ≥ grade 2 acute radiation dermatitis, esophagitis and pneumonitis were 19.3%, 4.5% and 2.6%, respectively. With a median follow-up time of 20.5 months (range: 9.9-41.8 months), 2 cases of chest wall recurrence, 2 regional lymph node recurrence, 6 distant metastases and 1 death were reported. Conclusions:When hypofractionated internal mammary chain is irradiated by electrons after mastectomy, the doses to the lung, heart and coronary artery are low, and the acute toxicities are mild. However, the dose to CTV im1 is inadequate. Although short-term efficacy is high, long-term follow-up is warranted.

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Breast implants are associated with well-known common complications that have been widely studied, such as rupture and capsular contraction. However, the increasingly growing number of patients with breast implants has led to the increased likelihood of coming across less common complications; these include seromas or late infection; adenopathies in the internal mammary chain; granulomas in the capsule of the implant, which in some cases can extend beyond the fibrous capsule; desmoid tumors associated with the implants; and breast implant-associated large cell anaplastic lymphoma. This article aims to review the main uncommon complications associated with breast implants and to describe and illustrate their findings in different imaging techniques. Proper management of these complications is important; this is especially true of late seroma and the diagnosis of breast implant-associated large cell anaplastic lymphoma for their repercussions.

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BACKGROUND AND PURPOSE: Breast cancer patients treated with radiotherapy are at increased risk of subsequent acute coronary syndromes (ACS). We aimed to study if radiotherapy also influences the prognosis of these ACS. MATERIALS AND METHODS: We included all 398 patients diagnosed with ACS following radiotherapy from our hospital-based cohort of early breast cancer patients aged <71 years, treated 1970-2009. Cardiovascular disease incidence and cause of death were acquired through questionnaires to general practitioners and cardiologists. Internal mammary chain (IMC) irradiation delivers the highest heart doses in breast cancer radiotherapy. Hence, we compared ACS prognosis between patients treated with/without IMC-irradiation. ACS prognosis was assessed through cardiac death, death due to ACS and cardiovascular disease incidence, using multivariable Cox proportional hazard models and by estimating cumulative incidence. RESULTS: In total, 62% of patients with ACS had received IMC-irradiation and 38% did not (median age at ACS diagnosis, 67 years). Median time between breast cancer and ACS was 15 years. After ACS, ten-year cumulative risk of cardiac death was 35% for patients who had IMC-irradiation (95% confidence interval [95%CI] 29-41) compared to 24% (95%CI 17-31) for patients without IMC-irradiation (p = 0.04). After correction for confounders, IMC-irradiation remained associated with a less favourable prognosis of ACS compared to no IMC-irradiation (hazard ratio cardiac death = 1.7, 95%CI 1.1-2.5). CONCLUSION: Our results suggest that radiotherapy, in case of substantial heart doses,may worsen ACS prognosis. This is an important, novel finding that may impact upon the risk-based care for breast cancer survivors with ACS.

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AIMS: Evidence has emerged that internal mammary chain (IMC) radiotherapy reduces breast cancer mortality, leading to changes in treatment guidelines. This study investigated current IMC radiotherapy criteria and the percentages of patients irradiated for breast cancer in England who fulfilled them. MATERIALS AND METHODS: A systematic search was undertaken for national guidelines published in English during 2013-2018 presenting criteria for 'consideration of' or 'recommendation for' IMC radiotherapy. Patient and tumour variables were collected for patients who received breast cancer radiotherapy in England during 2012-2016. The percentages of patients fulfilling criteria stipulated in each set of guidelines were calculated. RESULTS: In total, 111 729 women were recorded as receiving adjuvant breast cancer radiotherapy in England during 2012-2016 and full data were available on 48 095 of them. Percentages of patients fulfilling IMC radiotherapy criteria in various national guidelines were: UK Royal College of Radiologists 13% (6035/48 095), UK National Institute for Health and Care Excellence 18% (8816/48 095), Germany 32% (15 646/48 095), Ireland 56% (26 846/48 095) and USA 59% (28 373/48 095). Differences between countries occurred because in Ireland and the USA, treatment may be considered in some node-negative patients, whereas in the UK, treatment is considered if at least four axillary nodes are involved or for high-risk patients with one to three positive nodes. In Germany, treatment may be considered for all node-positive patients. CONCLUSIONS: There is substantial variability between countries in criteria for consideration of IMC radiotherapy, despite guidelines being based on the same evidence. This will probably lead to large variations in practice and resource needs worldwide.

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Adjuvant radiation therapy in breast cancer is a standard of care, either post-lumpectomy or in case of lymph node involvement. Internal mammary chain (IMC) is more and more included in the clinical target volume, because it increases overall survival. This increase must be weighed against cardiac complications in left breast cancer. Intensity modulated radiation therapy (IMRT) is used in this indication in order to better cover target volumes, but tends to increase irradiated healthy volumes, including the heart. The average cardiac dose is higher with IMRT, while it is also predictive of cardiovascular events in patients treated in 3D. This article aims to make an inventory of the IMC irradiations, as well as a review of the mechanisms of radiation-induced cardiac toxicity and ways to diagnose it early. Cooperation between medical oncologists, radiotherapy oncologists and cardiologists is needed to better support patients.

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OBJECTIVE: To evaluate the incidental coverage dose to the internal mammary nodes (IMN) in patients treated with postmastectomy radiotherapy (PMRT) and its relationship with the treatment plan. PATIENTS AND METHODS: We retrospectively analyzed 138 patients undergoing PMRT and divided them into three groups: three-dimensional conformal radiotherapy (3D-CRT), field-in-field forward intensity-modulated radiotherapy (F-IMRT), and inverse intensity-modulated radiotherapy (I-IMRT). The IMN were contoured according to the Radiation Therapy Oncology Group consensus and not included in the planning target volume. We analyzed incidental IMN dose coverage and its relationship with the lung and heart. RESULTS: The mean dose (Dmean) to the IMN was 32.85 Gy for all patients, and the dose delivered to the IMN showed no differences in 3D-CRT, F-IMRT, and I-IMRT (33.80, 29.65, and 32.95 Gy, respectively). In addition, 10.42%, 2.04%, and 9.76% of patients achieved ≥45 Gy with 3D-CRT, F-IMRT, and I-IMRT, respectively. No differences were evident among the three treatment plans regarding IMN dose in the first three intercostal spaces (ICS1-3). The Dmean, V20, V30, V40, and V50 of ICS2 and ICS3 were superior to those of ICS1 for all three plans. For 3D-CRT, a moderate positive correlation was evident between the Dmean to the IMN and the Dmean to the heart. For F-IMRT and I-IMRT, positive correlations were evident between the Dmean of the IMN and the Dmean and V20 of the lung. CONCLUSION: The mean incidental dose to the IMN for IMRT (F-IMRT and I-IMRT) and 3D-CRT after modified radical mastectomy was insufficient to treat subclinical disease. A substantial dose was delivered to the IMN in some patients. Higher incidental doses to the IMN were associated with a higher heart mean dose for 3D-CRT and a higher dose to the lung for IMRT. Future prospective studies should further explore subgroups that do not require IMN irradiation.

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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.

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AIM: The present study evaluated the increment of cardiac risk (CR) and absorbed dose in radiotherapy of the internal mammary chain (IMC), in particular with photon portals of 4 6 MV, and cobalt therapy (Co60); and, electron portals of 8, 12 and 16 MeV applied in the left breast, considering the adoption of a combined photon (16 Gy) and electron (30 Gy) protocols. MATERIALS AND METHODS: The modified ICRP-reference female model of 60 kg, 163 cm and 43 years of age, coil RCP-AF, was modelled. The MCNP6/SICODES codes were employed, where the spatial dose distributions and dose-volume histograms were generated. Toxicity limits and a CR model were considered. RESULTS: CR associated with the 6 MV, 4 MV and Co60 portals increased 41.1; 40.6 and 34.5%, respectively; while, in 8, 12 and 16 MeV portals, they were 5.0, 32.5 and 49.2%, respectively. High anomalous scatter radiation from electron portals was found in the left lung providing an average dose of 3.3-5.0 Gy. CONCLUSIONS: To RCP-AF, the Co60 portal for IMC-RT presented more attractive dose distribution, whose 16 Gy for photon-component produced less CR increase, 5% lower than the other photon portals. Considering electron portals, the smallest CR increase was produced by 8 MeV portal while 12-16 MeV made the risk higher. There is a call for a less hardened energetic spectrum in order to reduce CR; however, holding suitable IMC penetration. A combined Co60/8-12 MeV may bring benefits, reducing CR. The lowest risk was found to 46 Gy electron portals exclusively.

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AIMS: Radiotherapy target volumes in early breast cancer treatment increasingly include the internal mammary chain (IMC). In order to maximise survival benefits of IMC radiotherapy, doses to the heart and lung should be minimised. This dosimetry study compared the ability of three-dimensional conformal radiotherapy, arc therapy and proton beam therapy (PBT) techniques with and without breath-hold to achieve target volume constraints while minimising dose to organs at risk (OARs). MATERIALS AND METHODS: In 14 patients' datasets, seven IMC radiotherapy techniques were compared: wide tangent (WT) three-dimensional conformal radiotherapy, volumetric-modulated arc therapy (VMAT) and PBT, each in voluntary deep inspiratory breath-hold (vDIBH) and free breathing (FB), and tomotherapy in FB only. Target volume coverage and OAR doses were measured for each technique. These were compared using a one-way ANOVA with all pairwise comparisons tested using Bonferroni's multiple comparisons test, with adjusted P-values ≤ 0.05 indicating statistical significance. RESULTS: One hundred per cent of WT(vDIBH), 43% of WT(FB), 100% of VMAT(vDIBH), 86% of VMAT(FB), 100% of tomotherapy FB and 100% of PBT plans in vDIBH and FB passed all mandatory constraints. However, coverage of the IMC with 90% of the prescribed dose was significantly better than all other techniques using VMAT(vDIBH), PBT(vDIBH) and PBT(FB) (mean IMC coverage ± 1 standard deviation = 96.0% ± 4.3, 99.8% ± 0.3 and 99.0% ± 0.2, respectively). The mean heart dose was significantly reduced in vDIBH compared with FB for both the WT (P < 0.0001) and VMAT (P < 0.0001) techniques. There was no advantage in target volume coverage or OAR doses for PBT(vDIBH) compared with PBT(FB). CONCLUSIONS: Simple WT radiotherapy delivered in vDIBH achieves satisfactory coverage of the IMC while meeting heart and lung dose constraints. However, where higher isodose coverage is required, VMAT(vDIBH) is the optimal photon technique. The lowest OAR doses are achieved by PBT, in which the use of vDIBH does not improve dose statistics.

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