Left Breast Irradiation Research Articles

Dosimetric and radiobiological advantages from deep inspiration breath-hold and free breath technique for left-sided breast radiation using 3DCRT, IMRT and Rapid Arc methods-a complete assessment.

The verification and use of the best treatment approach using 3D conformal radiation therapy (3DCRT), intensity modulated radiation therapy (IMRT) and Rapid Arc methods for left breast radiation with dosimetric and radiobiological characteristics. The use of custom-built Python software for the estimation and comparison of volume, mean dose, maximum dose, monitor units and normal tissue integral dose along with radiobiological parameters such as NTCP, tumor control probability, equivalent uniform dose and LKB's effective volume from 3DCRT, IMRT and Rapid Arc planning with deep inspiration with breath holding (DIBH) and free breadth (FB) techniques. Volume growth of three-fourth in DIBH compared with FB causes a decrease in cardiac doses and complications because the left lung expands, pulling the heart away from the chest wall and the treatment area. A tiny area of the left lung was exposed during treatment, which reduced the mean dose. There was little difference in the treatment approaches because the spinal cord was immobile in both techniques. Rapid Arc is the unmatched modality for left-sided breast irradiation with significant patient breath-hold, as shown by the comparison of dosimetric and radiobiological parameters from treatment techniques with a deep inspiration breath-hold approach.

Cardiac Dysfunction Among Breast Cancer Survivors: Role of Cardiotoxic Therapy and Cardiovascular Risk Factors.

Cardiac dysfunction is the leading cause of mortality among 10-year breast cancer survivors. Limited information regarding long-term risks of cardiac dysfunction after cardiotoxic therapy (anthracyclines, trastuzumab/pertuzumab, radiation) has precluded development of surveillance guidelines for the survivors. Patients with breast cancer who completed cardiotoxic therapy underwent echocardiographic screening every 2 years. New-onset cardiac dysfunction was defined as left ventricular ejection fraction (LVEF) <50% after cardiotoxic therapy initiation and included early- and late-onset cardiac dysfunction. We evaluated 2,808 echocardiograms in 829 breast cancer survivors; the median age at breast cancer diagnosis was 54.2 years (range, 20.3-86.3); the median follow-up was 8.6 years (1.8-39.8); 39.7% received anthracyclines, 16% received trastuzumab/pertuzumab, 6.2% received both anthracyclines and trastuzumab/pertuzumab, and 38.1% received radiation alone. The cumulative incidence of cardiac dysfunction increased from 1.8% at 2 years to 15.3% at 15 years from cardiotoxic therapy initiation. Multivariable Cox regression analysis identified the following risk factors: non-Hispanic Black race (hazard ratio [HR], 2.15 [95% CI], 1.37 to 3.38), cardiotoxic therapies (anthracyclines: HR, 2.35 [95% CI, 1.25 to 4.4]; anthracyclines and trastuzumab/pertuzumab: HR, 3.92 [95% CI, 1.74 to 8.85]; reference: left breast radiation alone), selective estrogen receptor modulators (HR, 2.0 [95% CI, 1.2 to 3.33]), and precancer hypertension (HR, 3.16 [95% CI, 1.63 to 6.1]). Late-onset cardiac dysfunction was most prevalent among anthracycline- and radiation-exposed patients; early-onset cardiac dysfunction was most prevalent among patients exposed to anthracyclines and trastuzumab/pertuzumab; equal prevalence of both early- and late-onset cardiac dysfunction was observed in trastuzumab-/pertuzumab-exposed patients. Adjusted longitudinal analyses revealed an annual decline in LVEF by 0.29% (P = .009) over 20 years from breast cancer diagnosis. These findings provide evidence to support echocardiographic surveillance for several years after cardiotoxic therapy and also suggest a need to examine the efficacy of management of cardiovascular risk factors to mitigate risk.

Dose delivery error from respiratory motion in free breathing left breast irradiation

PurposeMany institutions worldwide currently deliver left breast radiotherapy in free breathing mode, mostly due to the unavailability of a Deep Inspiration Breath Hold technique (DIBH). This study aims at quantifying the error in dose delivery (compared to treatment plan) due to respiratory motion in free breathing irradiation of left breast or chest wall. Since subfields often consist in small, fine-tuned, highly targeted fields, slight intrafractional target motion may compromise their subtle benefit. Thus we analyzed the respiratory motion effect on target dose coverage, dose homogeneity and left lung dose. MethodsTreatment plans for twenty left breast or chest wall cancer patients previously treated at our center were retrieved and retrospectively planned with the introduction of an appropriate shift in isocenter location to simulate free breathing target motion. ResultsNo clinically significant dosimetric changes were found in all twenty cases when breathing motion was accounted for. Changes in target dose coverage (V95%), in target maximum dose (D2%) and in V20Gy lung dose were respectively less than 1.5%, 0.3% and 2.6%. ConclusionThe findings suggest that breast irradiation in free breathing mode does not undermine the dosimetric merits of the field-in-field technique and does not produce clinically significant dosimetric differences in dose delivery for target and lung compared to plan.

Abstract PO2-22-03: Reirradiation for locally recurrent breast cancer: a long-term single centre experience

Abstract Background: About 10–15% of patients with breast cancer will eventually develop an ipsilateral breast recurrence. The management of cancer relapse in previously irradiated tissues is a challenging therapeutic issue, and data on breast re-irradiation are currently lacking. Hence, the aim of this work was to report our experience with breast re-irradiation for non-metastatic recurrent breast cancer. Material and Methods: All patients who underwent a breast or chest wall re-irradiation in the Institut Curie, Paris, France between 2003 and 2019 were identified. Those who underwent re-irradiation only in other volumes than the ipsilateral breast were excluded. Local recurrence-free (LRFS), overall survival (OS), disease-specific survival (DSS), progression-free survival (PFS), and metastasis-free survival (MFS) were evaluated. Physician-reported acute and late toxicities were assessed using the Common Terminology Criteria for Adverse Events (CTCAE) 5.0. Results: Between 2003 and 2019, 21.372 patients underwent a breast irradiation in our institution. Of these, 453 received a new irradiation to the controlateral breast and/or lymph nodes, 105 to the homolateral lymph nodes without breast/chest wall re-irradiation and 28 received a second course of radiotherapy (RT) to the homolateral breast. These 28 patients were included in this study. Median follow up after re-irradiation was 45.5 months (IQR 33.5-79.75 months). The median age at the time of second breast RT was 63 years (IQR, 49-78). The median RT dose to the breast/chest wall was 60 Gy (interquartile range (IQR) 50-66 Gy) for the first irradiation and 48 Gy (IQR 30-50 Gy) for the second. The median cumulative dose was 100 Gy (IQR 92-114 Gy). The median time between the two courses of RT was 47 months (IQR 22.75-109.5 months). Eighteen (64%) patients were treated with a curative intent and 10 (36%) for palliative purposes. Ten (36%) had a macroscopic breast residue at re-irradiation. The second RT course was performed with electrons, photons and a combination of both in 13 (46%), 8 (29%) and 6 (21%) patients, respectively. At 2 years, LRFS, OS, DSS, PFS and MFS were respectively 59%, 79%, 82%, 50% and 75% in the whole cohort. 2-year-LRFS (72% vs 31%, p=0.02), OS (94% vs 50%, p&amp;lt; 0.01), DSS (94% vs 56%, p&amp;lt; 0.01) and PFS (61% vs 20%, p=0.02) differed significantly between patients treated in a curative or in a palliative intent, but not MFS (78% vs 69%, p=0.77). Among patients, 8 (29%) remained relapse-free 5 years after the second course of RT. Only one patient experienced an acute grade 3 adverse event (dermatitis), and 1 presented a late grade 3 one (skin fibrosis). One patient with major cardiovascular risk factors died of myocardial infarction 13 months after the second left breast irradiation. Conclusion: Breast or chest wall re-irradiation appears to be feasible with good disease control in patients treated with a curative intent, and acceptable toxicity rates. In addition, a significant number of patients were disease-free 5 years after the second course of RT. Prospective larger data with longer follow-up are needed to confirm these findings. Citation Format: Jérémy Baude, Rémi Dendale, Alain Fourquet, Youlia Kirova. Reirradiation for locally recurrent breast cancer: a long-term single centre experience [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-22-03.

Abstract PO2-20-11: Safety and efficacy of KEYNOTE-522 in combination with anti-retroviral therapy in a patient with HIV and triple-negative breast cancer

Abstract Introduction: Triple-negative breast cancer (TNBC) is a subtype of breast cancer (BC) that does not express estrogen receptor (ER), progesterone receptor (PR), or human epidermal growth factor receptor 2 (HER-2), accounting for about 15% of all BC. TNBC is more aggressive than other BC with a higher risk of recurrence and mortality. The current standard of care for high-risk, early-stage TNBC based on the KEYNOTE-522 trial is neoadjuvant multidrug chemotherapy (paclitaxel and carboplatin [TCb] weekly x 12 weeks and doxorubicin and cyclophosphamide [AC] Q3 weeks) with pembrolizumab (P). The trial demonstrated patients who received chemotherapy plus P had a higher pathological complete response and event-free survival compared to patients who received chemotherapy plus placebo. However, the trial excluded patients with any autoimmune disease requiring treatment within 2 years, a diagnosis of immunodeficiency or steroids within 7 days before the first treatment, or a known history of human immunodeficiency virus (HIV). While limited data exist on immune checkpoint inhibitors (ICI) in patients with immunodeficiencies, subsequent data demonstrate that patients with HIV have similar efficacy and immune-related adverse events (irAE) compared to patients without HIV, and 2017 consensus recommendations encouraged broader eligibility in clinical trials to include patients with HIV. We present one of the first reported clinical cases of a patient with HIV diagnosed with stage IIB TNBC, treated per KEYNOTE-522 and anti-retroviral therapy (ART). Clinical Case: A 55-year-old female with a medical history significant for HIV, self-detected a mass in her left breast. Diagnostic imaging demonstrated a suspicious 4.0 cm mass in the left breast without adenopathy. An ultrasound-guided biopsy of the mass revealed grade 3 invasive ductal carcinoma with ER 0%, PR &amp;lt; 1%, and HER-2 1+. The clinical stage was cT2N0M0, prognostic stage IIB. Genetic testing was positive for germline BRCA2 pathogenic variant. HIV PCR &amp;lt; 20 copies/mL and CD4 count 1.298 K/uL prior to neoadjuvant chemotherapy. The patient was adherent to HIV ART with bictegravir, emtricitabine, and tenofovir alafenamide. The patient received KEYNOTE-522, including 11 cycles of TCb-P, followed by four cycles of AC-P. Following neoadjuvant treatment, the patient underwent a left segmental mastectomy and sentinel lymph node biopsy and achieved a pathological complete response. She completed left whole breast radiation (RT) with 3DCRT plus 3DCRT tumor bed boost to a total dose of 48.06 cGy and one-year of adjuvant P. Treatment-related adverse events included grade 4 febrile neutropenia after cycle one AC without growth factor, requiring a 5-day hospitalization; and grade 3 peripheral neuropathy, resulting in discontinuation of week 12 of TCb. The patient also developed paronychia, and a pulmonary embolism after week 11 of TCb. She had no irAE. Radiation-related adverse events included grade 1 left breast dermatitis and fatigue and mild left breast soreness. Discussion: Among the subset of patients diagnosed with TNBC, the percentage of patients with HIV or immunodeficiency receiving active BC treatment is low. Safety and efficacy data for novel cancer therapeutics including ICI are limited since historically patients with HIV and other immunodeficiency states were excluded from trials. Anti-PD-1 ICI has become a key part of the standard of care for the treatment of breast cancer. Patients with HIV experience rare infectious complications and have a life expectancy near the general population with ART. We support the inclusion of patients with HIV in future clinical trials for TNBC and/or ICI and recommend treatment of patients with HIV and TNBC per standard of care in multi-disciplinary collaboration with HIV clinicians. Citation Format: Stephanie Haddad, Stephanie Graff, Matthew Hadfield, Yihong Wang, Charu Taneja, Kara Leonard, Martha Sanchez, Robert Ward, Ana Lourenco, Mary Anne Fenton. Safety and efficacy of KEYNOTE-522 in combination with anti-retroviral therapy in a patient with HIV and triple-negative breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-20-11.

3131: Development of an automated VMAT-technique for left locoregional breast radiotherapy including IMN

3131: Development of an automated VMAT-technique for left locoregional breast radiotherapy including IMN

1568: Toward multi-institutional Knowledge-Based benchmark for right and left whole breast irradiation

1568: Toward multi-institutional Knowledge-Based benchmark for right and left whole breast irradiation

Inter-institutional variability of knowledge-based plan prediction of left whole breast irradiation

PurposeWithin a multi-institutional project, we aimed to assess the transferability of knowledge-based (KB) plan prediction models in the case of whole breast irradiation (WBI) for left-side breast irradiation with tangential fields (TF). MethodsEight institutions set KB models, following previously shared common criteria. Plan prediction performance was tested on 16 new patients (2 pts per centre) extracting dose-volume-histogram (DVH) prediction bands of heart, ipsilateral lung, contralateral lung and breast. The inter-institutional variability was quantified by the standard deviations (SDint) of predicted DVHs and mean-dose (Dmean). The transferability of models, for the heart and the ipsilateral lung, was evaluated by the range of geometric Principal Component (PC1) applicability of a model to test patients of the other 7 institutions. ResultsSDint of the DVH was 1.8 % and 1.6 % for the ipsilateral lung and the heart, respectively (20 %-80 % dose range); concerning Dmean, SDint was 0.9 Gy and 0.6 Gy for the ipsilateral lung and the heart, respectively (<0.2 Gy for contralateral organs). Mean predicted doses ranged between 4.3 and 5.9 Gy for the ipsilateral lung and 1.1–2.3 Gy for the heart. PC1 analysis suggested no relevant differences among models, except for one centre showing a systematic larger sparing of the heart, concomitant to a worse PTV coverage, due to high priority in sparing the left anterior descending coronary artery. ConclusionsResults showed high transferability among models and low inter-institutional variability of 2% for plan prediction. These findings encourage the building of benchmark models in the case of TF-WBI.

Individual benefit in heart sparing during DIBH-supported left breast radiotherapy

IntroductionDeep-inspirational breath hold (DIBH) is an option for heart protection in breast radiotherapy; we intended to study its individual benefit. Materials and Methods3DCRT treatment planning was performed in a cohort of 103 patients receiving radiotherapy of the whole breast (WBI)/chest wall (CWI) ± nodal regions (NI) both under DIBH and free breathing (FB) in the supine position, and in the WBI only cases prone (n = 45) position, too. A series of patient-related and heart dosimetry parameters were analyzed. ResultsThe DIBH technique provided dramatic reduction of all heart dosimetry parameters the individual benefit, however, varied. In the whole population the best predictor of benefit was the ratio of ipsilateral lung volume (ILV)FB and ILVDIBH. In the WBI cohort 9–11 patients and 5–8 patients received less dose to selected heart structures with the DIBH and prone positioning, respectively; based on meeting various dose constraints DIBH was the only solution in 6–13 cases, and prone positioning in 5–6 cases. In addition to other excellent predictors, a small ILVFB or ILVDIBH with outstanding predicting performance (AUC ≥ 0.90) suggested prone positioning. Detailed analysis consistently indicated the outstanding performance of ILVFB and ILVDIBH in predicting the benefit of one over the other technique in lowering the mean heart dose (MHD), left anterior descending coronary artery (LAD) mean dose and left ventricle(LV)-V5Gy. The preference of prone positioning was further confirmed by anatomical parameters measured on a single CT scan at the middle of the heart. Performing spirometry in a cohort of 12 patients, vital capacity showed the strongest correlation with ILVFB and ILVDIBH hence this test could be evaluated as a clinical tool for patient selection. DiscussionIndividual lung volume measures estimated by spirometry and anatomical data examined prior to acquiring planning CT may support the preference of DIBH or prone radiotherapy for optimal heart protection.

Continuous Positive Airway Pressure–Assisted Breathing With Supine Tangential Left Breast Radiation Therapy When Deep Inspiration Breath-Hold Radiation Therapy Was Ineffective or Unsuitable: Clinical Implications for an Affordable Heart-Sparing Breast Radiation Therapy to Reduce the Health Care Disparities in Low-Resource Settings

Continuous Positive Airway Pressure–Assisted Breathing With Supine Tangential Left Breast Radiation Therapy When Deep Inspiration Breath-Hold Radiation Therapy Was Ineffective or Unsuitable: Clinical Implications for an Affordable Heart-Sparing Breast Radiation Therapy to Reduce the Health Care Disparities in Low-Resource Settings

Impact of Dose Calculation Algorithms and Radiobiological Parameters on Prediction of Cardiopulmonary Complications in Left Breast Radiation Therapy.

Breast cancer requires evaluating treatment plans using dosimetric and biological parameters. Considering radiation dose distribution and tissue response, healthcare professionals can optimize treatment plans for better outcomes. This study aimed to evaluate the effects of the different Dose Calculation Algorithms (DCAs) and Biologically Model-Related Parameters (BMRPs) on the prediction of cardiopulmonary complications due to left breast radiotherapy. In this practical study, the treatment plans of 21 female patients were simulated in the Monaco Treatment Planning System (TPS) with a prescribed dose of 50 Gy in 25 fractions. Dose distribution was extracted using the three DCAs [Pencil Beam (PB), Collapsed Cone (CC), and Monte Carlo (MC)]. Cardiopulmonary complications were predicted by Normal Tissue Complication Probability (NTCP) calculations using different dosimetric and biological parameters. The Lyman-Kutcher-Burman (LKB) and Relative-Seriality (RS) models were used to calculate NTCP. The endpoint for NTCP calculation was pneumonitis, pericarditis, and late cardiac mortality. The ANOVA test was used for statistical analysis. In calculating Tumor Control Probability (TCP), a statistically significant difference was observed between the results of DCAs in the Poisson model. The PB algorithm estimated NTCP as less than others for all Pneumonia BMRPs. The impact of DCAs and BMRPs differs in the estimation of TCP and NTCP. DCAs have a stronger influence on TCP calculation, providing more effective results. On the other hand, BMRPs are more effective in estimating NTCP. Consequently, parameters for radiobiological indices should be cautiously used s to ensure the appropriate consideration of both DCAs and BMRPs.

Cardiac protective techniques in left breast radiotherapy: rapid selection criteria for routine clinical decision making

ObjectiveIn left breast radiotherapy (RT) desired heart doses may be achieved without heart-sparing RT techniques in some patients. We aimed to examine the existence of predictive factors and cutoff points to determine which patients are the main candidates for heart-sparing RT techniques.Material and methodDosimetric data for left breast cancer was examined. RT plans were made at conventional doses to the breast and peripheral lymph nodes. Statistical analyses were performed using SPSS 22.0 (SPSS Inc., IBM Corp., Armonk, NY).Result114 cases were evaluated by ROC (Receiver operating characteristic) analysis in the breast-conserving surgery (BCS) and mastectomy groups. While only left lung volume (AUC: 0.74, 95% CI 0.61–0.87, p = 0.002) was significant in BCS cases, in cases with mastectomy, left lung volume (AUC: 0.81, 95% CI 0.69–0.94, p = 0.002) and lung/heart volume ratio (AUC: 0.83, 95% CI 0.70–0.96, p = 0.001) had a significant relationship with the relevance of heart doses. The cutoff point of 1.92 was selected for the lung/heart volume ratio for the mastectomized patients. Moreover, the cutoff point 1154 cc and 1208 cc was determined for the left lung volume for the BCS and mastectomized patients, respectively.ConclusionVarious cutoff points in left breast RT can be used to predict whether RT plans will meet QUANTEC (Quantitative Analysis of Normal Tissue Effects in the Clinic) heart dose limits. Evaluating only these few cutoff points before planning makes it possible to eliminate 70% of patients with BCS and 40% of patients with mastectomy from respiratory-controlled methods, which require time and effort. Patients with lung volume and lung/heart volume ratio smaller than the cutoff values can be considered primary candidates for heart-sparing techniques.

Technical note: Clinical evaluation of a newly released surface-guided radiation therapy system on DIBH for left breast radiation therapy.

It has been shown that a significant reduction of mean heart dose and left anterior descending artery (LAD) dose can be achieved through the use of DIBH for left breast radiation therapy. Surface-guided DIBH has been widely adopted during the last decade, and there are mainly three commercially available SGRT systems. The reports of the performance of a newly released SGRT system for DIBH application are currently very limited. To evaluate the clinical performance of a newly released SGRT system on DIBH for left breast radiation therapy. Twenty-five left breast cancer patients treated with DIBH utilizing Varian's Identify system were included (total 493-fraction treatments). Four aspects of the clinical performance were evaluated: Identify offsets of free breathing post patient setup from tattoos, Identify offsets during DIBH, Identify agreement with radiographic ports during DIBH, and DIBH reference surface re-capture post patient shifts. The systematic and random errors of free breathing Identify offsets post patient setup were calculated for each patient, as well as for offsets during DIBH. Radiographic ports were taken when the patient's DIBH position was within the clinical tolerance of (±0.3cm,±30 ), and these were then compared with treatment field DRRs. If the ports showed that the patient alignment did not agree with the DRRs within 3mm, a patient shift was performed. A new reference surface was captured and verification ports were taken. The all-patient average systematic and random errors of Identify offsets for free breathing were within (0.4cm, 1.50 ) post tattoo setup. The maximum per-patient systematic and random errors were (1.1cm, 6.20 ) and (0.9cm, 20 ), and the maximum amplitude of Identify offsets were (2.59cm, 90 ). All 493-fraction DIBH treatments were delivered and successfully guided by the Identify SGRT system. The systematic and random errors of Identify offsets for DIBH were within (0.2cm, 2.30 ). Seven patients needed re-captured surface references due to surface variation or position shifts based on the ports. All patient DIBH verification ports guided by Identify were approved by attending physicians. This evaluation showed that the Identify system performed effectively for surface-guided patient setup and surface-guided DIBH imaging and treatment delivery. The feature of color-coded real-time patient surface matching feedback facilitated the evaluation of the patient alignment accuracy and the adjustment of the patient position to match the reference.

Can we predict the cardiac benefit of deep inspiration breath hold for left breast and regional nodal irradiation?

PurposeDeep inspiration breath hold (DIBH) is used to decrease the dose of radiotherapy delivered to the heart. There is a need to define criteria to select patients with the potential to derive a real clinical benefit from DIBH treatment. Our study's main goal was to investigate whether two CT-scan cardiac anatomical parameters, cardiac contact distance in the parasagittal plane (CCDps) and lateral heart-to-chest distance (HCD), were predictive of unmet dosimetric cardiac constraints for left breast and regional nodal irradiation (RNI). Materials and methodsThis retrospective single-institution dosimetric study included 62 planning CT scans of women with left-sided breast cancer (BC) from 2016 to 2021. Two independent radiation oncologists measured HCD and CCDps twice to assess inter- and intra-observer reproducibility. Dosimetric constraints to be respected were defined, and dosimetric parameters of interest were collected for each patient. ResultsMean heart dose was 7.9Gy. Inter-rater reproducibility between the two readers was considered excellent. The mean heart dose constraint<8Gy was not achieved in 25 patients (40%) and was achieved in 37 patients (60%). There was a significant correlation between mean heart dose and HCD (rs=–0.25, P=0.050) and between mean heart dose and CCDps (rs=0.25, P=0.047). The correlation between HCD and CCDps and unmet cardiac dosimetric constraints was not statistically significant. ConclusionOur dosimetric analysis did not find that the cardiac anatomical parameters HCD and CCDps were predictive of unmet dosimetric cardiac constraints, nor that they were good predictors for cardiac exposure in left-sided BC radiotherapy comprising RNI.

Dosimetric Evaluation of Cardiac Structures on Left Breast Cancer Radiotherapy: Impact of Movement, Dose Calculation Algorithm and Treatment Technique.

Breast cancer is the most frequently diagnosed and leading cause of cancer-related deaths among females. The treatment of breast cancer with radiotherapy, albeit effective, has been shown to be toxic to the heart, resulting in an elevated risk of cardiovascular disease and associated fatalities. In this study, we evaluated the impact of respiratory movement, treatment plans and dose calculation algorithm on the dose delivered to the heart and its substructures during left breast radiotherapy over a cohort of 10 patients. We did this through three image sets, four different treatment plans and the employment of three algorithms on the same treatment plan. The dose parameters were then employed to estimate the impact on the 9-year excess cumulative risk for acute cardiac events by applying the model proposed by Darby. The left ventricle was the structure most irradiated. Due to the lack of four-dimensional computed tomography (4DCT), we used a set of images called phase-average CT that correspond to the average of the images from the respiratory cycle (exhale, exhale 50%, inhale, inhale 50%). When considering these images, nearly 10% of the heart received more than 5 Gy and doses were on average 27% higher when compared to free breathing images. Deep inspiration breath-hold plans reduced cardiac dose for nine out of 10 patients and reduced mean heart dose in about 50% when compared to reference plans. We also found that the implementation of deep inspiration breath-hold would reduce the relative lifetime risk of ischemic heart disease to 10%, in comparison to 21% from the reference plan. Our findings illustrate the importance of a more accurate determination of the dose and its consideration in cardiologists' consultation, a factor often overlooked during clinical examination. They also motivate the evaluation of the dose to the heart substructures to derive new heart dose constraints, and a more mindful and individualized clinical practice depending on the treatment employed.

Comparison of cone beam computed tomography (CBCT)-based image guided radiotherapy approaches in the reduction of setup uncertainties during deep inspiration breath-hold radiotherapy (DIBH-RT) for left breast cancer

Advances in radiotherapy has allowed higher cure rates for cancer such as breast and thus, it is important to reduce the possible radiation side effects from exposure to other organs such as the heart. Deep inspiration breath-hold radiotherapy technique (DIBH-RT) significantly reduces cardiac dose during left breast radiotherapy, but the patient setup requires careful adoption of image guidance radiotherapy technique (IGRT) approaches. This study investigates the effectiveness of cone beam computed tomography (CBCT)-based IGRT protocols for patients' inter-fraction set-up correction. Setup error data from two patients’ groups; A and B who had daily CBCT and first 3 fractions + weekly CBCT imaging respectively, were analysed. This constitutes a total of 13 left breast cancer patients treated using DIBH-RT at Advanced Medical Dental Institute (AMDI), Universiti Sains Malaysia (USM), Malaysia. The analysis was performed using MATLAB (MathWorks Inc Natick MA) to calculate the mean setup errors. The population systematic (∑) and random (σ) errors were calculated for non-IGRT, online, and two offline IGRT protocols; no action level (NAL) and extended no action level (eNAL) for each patient group. The corresponding planning target volume (PTV) margin and its percentage reduction for each of the IGRT protocols were established using van Herk margin recipe. The least population systematic setup error and PTV margin were found when using the online protocol (∑X/Y/Z = 0.17/0.22/0.31 mm; PTVX/Y/Z = 0.71/0.92/1.28 mm) followed by eNAL (∑X/Y/Z = 1.32/1.94/1.85 mm; PTVX/Y/Z = 5.75/7.99/8.46 mm), NAL (∑X/Y/Z = 1.45/2.26/1.84 mm; PTVX/Y/Z = 6.27/8.93/8.46 mm) and non-IGRT (∑X/Y/Z = 2.28/3.35/3.10 mm; PTVX/Y/Z = 7.77/10.85/10.93 mm). Up to 90% in PTV margin reduction is achieved with the online protocol. In conclusion, the use of IGRT during DIBH-RT for left breast cancer patients reduces patient set-up error and allows the use of tighter PTV margins. The online IGRT protocol was shown to be more effective in the reduction of errors and the PTV margin followed by eNAL and NAL offline IGRT protocols.

Impact of breath hold on regional nodal irradiation and heart volume in field in left breast cancer adjuvant irradiation.

Compared to the free-breathing technique, adjuvant left breast irradiation after breast-conserving surgery or mastectomy using the breath-hold method significantly reduces the heart mean dose, Left anterior descending artery, and ipsilateral lung doses. Movement with deep inspiration may also reduce heart volume in the field and regional node doses. Pre-radiotherapy planning CT was performed in the free-breathing, and breath-hold techniques using RPM, demographic information, clinicopathological data, heart volume in the field, heart mean dose, LAD mean dose, and regional nodal doses were calculated in both free breathing and DIBH. Fifty patients with left breast cancer receiving left breast adjuvant radiation were enrolled. There was no significant difference in axillary LN coverage between the two techniques, except for SCL maximum dose, Axilla I node maximum dose, and Axilla II minimum dose in favor of the breath hold technique. The mean age was 47.54years, 78% had GII IDC, 66% had positive LVSI results, and 74% of patients had T2. The breath hold strategy resulted in considerably decreased mean heart dose (p = 0.000), LAD dose (p = 0.000), ipsilateral lung mean dose (p = 0.012), and heart volume if the field (p = 0.013). The mean cardiac dosage and the dose of the LAD were significantly correlated (p = 0.000, R = 0.673). Heart volume in the field and heart mean dosage was not significantly correlated (p = 0.285, r = -0.108). When compared to free breathing scans, DIBH procedures result in considerably reduced dosage to the OAR and no appreciable changes in dose exposure to regional lymph node stations in patients with left-sided breast cancer.

Robustness analysis of surface-guided DIBH left breast radiotherapy: personalized dosimetric effect of real intrafractional motion within the beam gating thresholds.

The robustness of surface-guided (SG) deep-inspiration breath-hold (DIBH) radiotherapy (RT) for left breast cancer was evaluated by investigating any potential dosimetric effects due to the residual intrafractional motion allowed by the selected beam gating thresholds. The potential reduction of DIBH benefits in terms of organs at risk (OARs) sparing and target coverage was evaluated for conformational (3DCRT) and intensity-modulated radiation therapy (IMRT) techniques. Atotal of 192 fractions of SGRT DIBH left breast 3DCRT treatment for 12patients were analyzed. For each fraction, the average of the real-time displacement between the isocenter on the daily reference surface and on the live surface ("SGRT shift") during beam-on was evaluated and applied to the original plan isocenter. The dose distribution for the treatment beams with the new isocenter point was then calculated and the total plan dose distribution was obtained by summing the estimated perturbed dose for each fraction. Then, for each patient, the original plan and the perturbed one were compared by means of Wilcoxon test for target coverage and OAR dose-volume histogram (DVH) metrics. Aglobal plan quality score was calculated to assess the overall plan robustness against intrafractional motion of both 3DCRT and IMRT techniques. Target coverage and OAR DVH metrics did not show significant variations between the original and the perturbed plan for the IMRT techniques. 3DCRT plans showed significant variations for the left descending coronary artery (LAD) and the humerus only. However, none of the dose metrics exceeded the mandatory dose constraints for any of the analyzed plans. The global plan quality analysis indicated that both 3DCRT and IMRT techniques were affected by the isocenter shifts in the same way and, generally, the residual isocenter shifts more likely tend to worsen the plan in all cases. The DIBH technique proved to be robust against residual intrafractional isocenter shifts allowed by the selected SGRT beam-hold thresholds. Small-volume OARs located near high dose gradients showed significant marginal deteriorations in the perturbed plans with the 3DCRT technique only. Global plan quality was mainly influenced by patient anatomy and treatment beam geometry rather than the technique adopted.

MAGNETIC RESONANCE IMAGING EVALUATION OF INCIDENTAL CARDIAC IRRADIATION DURING LEFT BREAST CANCER RADIOTHERAPY: A SYSTEMATIC REVIEW

Breast cancer is one of the most common malignant tumours among women. Radiotherapy plays a key role in the management of breast cancer patients. However, radiotherapy results in incidental exposure of the heart. This work systematically reviewed articles on magnetic resonance imaging (MRI) evaluation of cardiac changes due to incidental cardiac irradiation during left breast radiotherapy and also to identify the MRI sequences used during evaluation. A systematic literature search was conducted in the following three selected databases: PubMed, ScienceDirect and Scopus using carefully defined search terms related to the left breast, MRI and cardiac irradiation. The quality of the included papers was determined using the critical appraisal skills programme for qualitative studies. The review had a total of six articles that were screened and graded for quality. Articles graded as high and moderate in terms of quality assessment were included and characterised based on the sample size, type of cancer treated, treatment methods employed, and period MRI was performed after radiotherapy. The review showed that breast cancer patients who had radiotherapy also developed radiation-induced heart disease (RIHD) few months post treatment. The review noted that breast cancer patients receiving radiation treatment are at high risk of RIHD which may affect their quality of life after completion of treatment. Cardiac MRI facilitates early detection of RIHD, hence better patient management.

V5 and High Sensitivity Cardiac Troponin T for Early Detection of Cardiac Toxicity During Left Breast Cancer Irradiation.

The high sensitivity cardiac troponin T (Hs-cTnT) is a myocardial damage biomarker that could have a predictive value in patients who undergo radiotherapy for left sided breast cancer. The aim of this study was to evaluate the early effect of left whole breast radiotherapy (WB-RT) on serum Hs-cTnT levels and its correlation with pre-existing factors. The study was conducted from December 2017 to May 2018. Forty-five patients with early stage left-sided breast cancer who received adjuvant breast hypofractionated RT without prior chemotherapy were included. Serum levels of Hs-cTnT were obtained before, weekly during RT, and within one week after the end of treatment. Considering the physiological variations of serum levels, an increase in Hs-cTnT (∆Hs-cTnT) of more than 30% from the baseline value was chosen as a threshold. The main cardiovascular risk factors were recorded. Dose volume histograms (DVHs) were used to provide a quantitative analysis for the whole heart, left ventricle, and left anterior descending artery (LAD). Twelve of 45 patients (26.6%) showed a ∆Hs-cTnT ≥30%. The maximum Hs-cTnT level was recorded in the last week of treatment. ∆Hs-cTnT was strongly associated with heart V5 (p=0.05) and hypertension (p=0.05). Multivariate analysis confirmed the importance of the heart V5 and correlated with ∆Hs-cTnT. The increase in Hs-cTnT serum levels during adjuvant WB-RT suggested a correlation with the cardiac radiation dose in chemotherapy-naive breast cancer patients. A longer follow-up is needed to correlate Hs-cTnT values with cardiac events.