Internal Mammary Chain Research Articles

The Ghost Of Hip Arthroplasties Past: It Takes A Geriatrician To Mine For Metal

Abstract Background An 84-year-old female presented to Geriatric Medicine out-patient clinic with many years of persistent right hip pain, generalised myalgia; and several months of constipation, weight loss and persistent elevation of C-reactive protein and Erythrocyte Sedimentation Rate. The General Practitioner's concern was occult neoplasm. History of right hip arthroplasty in 2011. 6 years prior, she had wide local excision and adjuvant radiotherapy for a grade 3, “triple negative”, invasive ductal carcinoma of the right breast. Serial imaging identified a right parasternal, internal mammary chain neurofibroma. A Rheumatologist had administered intra-articular steroid to both glenohumeral joints for plain X-ray confirmed osteoarthritis, in the absence of serological vasculitic or autoimmune rheumatological disease. Benefit was transient. Her Oncologist had arranged MRI spine for “sciatica” demonstrating L3/4 and L4/5 stenosis and a large right adnexal cyst. Subsequently, the Gynaecology team assessed and planned interval MRI pelvis as initial MRI suggested a right partial hydrosalpinx, left internal chain lymphadenopathy and nodule adjacent to sacroiliac joint. Methods History, examination and imaging results were checked against the Medical Device Alert number 18 from the Medicines and Healthcare products Regulatory Agency (UK) in 2017. Oxford Hip Score Assessment was 29. Lymphatic drainage from medial hip joint is towards right iliac chain. Results In the absence of Gadolinium based contrast agents within 96hours, metal testing demonstrated: Serum Cobalt was 232nmol/L or 13.7 ug/L; Serum Chromium was 78.8nmol/L or 4.1ug/L; Chromium Urine: Creatinine Urine Ratio was 24.54nmol/mmol; and Cobalt Urine: Creatinine Urine Ratio73.96nmol/mmol. These elevated blood and urine results confirmed metal-on-metal hip disease. Conclusion Consider symptomatic metal-on-metal hip disease with soft-tissue involvement in patients presenting with post-hip arthroplasty joint pain, generalised myalgia and raised inflammatory markers; particularly if there is unexplained ipsilateral internal iliac chain lymphadenopathy and pelvic fluid collections. If confirmed, metalwork explanation is the treatment.

SIRARIS: Survey of internal mammary radiotherapy among radiation oncologists from Italy & Spain.

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. 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. 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. IMC radiotherapy indications remain controversial, with differences between Italian and Spanish oncologists.

Evaluation of Ethos intelligent optimization engine for left locally advanced breast cancer.

To evaluate the feasibility to use a standard Ethos planning template to treat left-sided breast cancer with regional lymph nodes. The tuning cohort of 5 patients was used to create a planning template. The validation cohort included 15 patients treated for a locally advanced left breast cancer randomly enrolled. The Ethos planning template was tuned using standard 3 partial arc VMAT and two collimator rotation configurations: 45/285/345° and 30/60/330°. Re-planning was performed automatically using the template without editing. The study was conducted with a schedule of 42.3 Gy in 18 fractions to the breast/chestwall, internal mammary chain (IMC) and regional lymph nodes ("Nodes"). The PTV was defined as a 3D extension of the CTV with a margin of 7mm, excluding the 5mm below the skin. The manual treatment plans were performed using Eclipse treatment planning system with AAA and PO algorithms (v15.6) and a manual arc VMAT configuration and imported in Ethos TPS (v1.1) for a dose calculation with Ethos Acuros algorithm. The automated plans were compared with the manual plans using PTV and CTV coverage, homogeneity and conformity indices (HI and CN) and doses to organs at risk (OAR) via DVH metrics. For each plan, the patient quality assurance (QA) were performed using Mobius3D and gamma index. Finally, two breast radiation oncologists performed a blinded assessment of the clinical acceptability of each of the three plans (manual and automated) for each patient. The manual and automated plans provided suitable treatment planning as regards dose constraints. The dosimetric comparison showed the CTV_breast D99% were significantly improved with both automated plans (p< 0,002) while PTV coverage was comparable. The doses to the organs at risk were equivalent for the three plans. Concerning treatment delivery, the Ethos-45° and Ethos-30° plans led to an increase in MUs compared to the manual plans, without affecting the beam on time. The average gamma index pass rates remained consistently above 98% regardless of the type of plan utilized. In the blinded evaluation, clinicians 1 and 2 assessed 13 out of 15 plans for Ethos 45° and 11 out of 15 plans for Ethos 30° as clinically acceptable. Using a standard planning template for locally advanced breast cancer, the Ethos TPS provided automated plans that were clinically acceptable and comparable in quality to manually generated plans. Automated plans also dramatically reduce workflow and operator variability.

Internal mammary lymphadenopathy in breast cancer: a narrative review and update.

While the axillary nodal basin is the most common lymphatic drainage pathway of the breast, the internal mammary (IM) lymph node chain plays a significant role in breast cancer staging and treatment. It has been identified as sentinel nodal drainage in approximately 13-37% of patients. Despite this, the data is still limited with regard to diagnosis and management when there is suspicion or confirmation of IM lymph node (IMLN) involvement by metastatic breast cancer. The objective of this publication is to provide a comprehensive assessment of the current body of literature surrounding the diagnosis, management and prognostic value of IMLNs in breast cancer treatment. Review of the literature published regarding IMLN diagnosis, significance, and management was completed in PubMed. Additional focus was placed on reviewing articles published within the past 10 years as foundation for an update regarding the current practice and future directions in this space. Improved imaging techniques, with positron emission tomography-computed tomography and magnetic resonance imaging, have led to increase in the identification of IM lymphadenopathy, yielding surgical staging of the IM nodes nearly obsolete. While IM nodal metastases may play a role in overall survival (OS), it has not been demonstrated to be an independent risk factor for increased locoregional recurrence. IM nodal irradiation (IMNI) therapy has been a mainstay in the treatment of IM disease in the context of breast cancer. IMNI has demonstrated improvement in OS and risk of distant recurrence. Wide variations in radiation practices for patients with IM lymphadenopathy exist internationally, highlighting the lack of clear data driven consensus guidelines. Herein, we provide an updated assessment of the current diagnosis, clinical significance, and management of IM lymphadenopathy for breast cancer patients.

DIBH reduces right coronary artery and lung radiation dose in right breast cancer loco-regional radiotherapy

To determine whether deep inspiratory breath-hold (DIBH) reduces dose to organs-at-risk (OAR), in particular the right coronary artery (RCA), in women with breast cancer requiring right-sided post-mastectomy radiotherapy (PMRT) including internal mammary chain (+IMC) radiotherapy (RT). Fourteen consecutive women requiring right-sided PMRT + IMC were retrospectively identified. Nodal delineation was in accordance with European Society for Radiology and Oncology (ESTRO) guidelines and tangential chest wall fields marked. Patients were planned with Anisotropic Analytical Algorithm using free-breathing (FB) and DIBH datasets. Dose was calculated using Acuros External Beam algorithm. FB and DIBH dose comparisons were analyzed for heart, RCA and right lung, as were chest wall and IMC planning target volumes (PTVs). DIBH vs FB resulted in median decreases of: the RCA mean dose by 0.6Gray (Gy) (interquartile range (IQR) 0.1, 1.9) (p = 0.002), RCA max dose by 1.8Gy (IQR 0.8, 6.1) (p = 0.002), and V5Gy by 2.9% (IQR 0.0, 37.2) (p = 0.016). RCA data indicated no statistically significant dosimetric reduction ≥10Gy. A median reduction of 1.7Gy (c -0.0, 7.1) (p = 0.019) in maximum heart dose was recorded with DIBH vs FB; no significant difference was observed in other heart and left anterior descending coronary artery parameters. The median reduction in right lung mean dose was 2.8Gy for DIBH vs FB plans (IQR 1.6, 3.6) (p = 0.001); significant median reductions of V5Gy, V20Gy, and V30Gy were all achieved with DIBH. Chest wall PTV coverage did not significantly differ between DIBH and FB plans; IMC dosimetric coverage improved with use of DIBH (V47.5Gy, V45Gy, V42Gy). DIBH reduced OAR dose in right-sided PMRT + IMC patients. A novel finding was that DIBH decreased RCA dose. Heart and right lung dose were also decreased with DIBH, whilst optimally dosed PTVs were maintained.

151 (PB-058) Poster - Predictive factors of incidental internal mammary chain irradiation in breast cancer radiotherapy

151 (PB-058) Poster - Predictive factors of incidental internal mammary chain irradiation in breast cancer radiotherapy

A Comparison of 3D Conformal and Deep Inspiratory Breath Holding vs. 4D-CT Intensity-Modulated Radiation Therapy for Patients with Left Breast Cancer.

Multimodality is required for the treatment of breast cancer. Surgery, radiation (RT), and systemic therapy were traditionally used. Pharmacotherapy includes different drug mechanisms, such as chemotherapy, hormone therapy, and targeted therapies, alone or in combination with radiotherapy. While radiation offers numerous benefits, it also has certain harmful risks. such as cardiac and pulmonary toxicity, lymphedema, and secondary cancer. Modern radiation techniques have been developed to reduce organs at risk (OAR) doses. This study is a prospective feasibility trial conducted at the Fayium Oncology Center on patients with left breast cancer receiving adjuvant locoregional radiotherapy after either breast conservative surgery (BCS) or modified radical mastectomy (MRM). This study aimed to assess the proportion of patients who are fit both physically and intellectually to undergo breast radiotherapy using the deep inspiratory breath-holding (DIBH) technique, comparing different dosimetric outcomes between the 3D dimensional conformal with DIBH and 4D-CT IMRT plans of the same patient. D95 of the clinical target volume (CTV) of the target is significantly higher in the 3D DIBH plan than in the IMRT plan, with an average of 90.812% vs. 86.944%. The dosimetry of the mean heart dose (MHD) in the 4D-CT IMRT plan was significantly lower than in the 3D conformal with the DIBH plan (2.6224 vs. 4.056 Gy, p < 0.0064), and no significant difference between the two plans regarding mean left anterior descending artery (LAD) (14.696 vs. 13.492 Gy, p < 0.58), maximum LAD (39.9 vs. 43.5 Gy, p < 0.35), and V20 of the ipsilateral lung (18.66% vs. 16.306%, p < 0.88) was observed. Internal mammary chain (IMC) irradiation was better in the 4D-CT IMRT plan. Radiotherapy of the breast and chest wall with the 4D-CT IMRT technique appears not to be inferior to the 3D conformal with the DIBH technique and can be used as an alternative to the 3D conformal with the DIBH technique in patients meeting the exclusion criteria for performing the DIBH maneuver concerning coverage to target volumes or unacceptably high doses to OAR.

Dose to Organ at Risk and its Characteristic Variation with the Clinically Used Different Prescription Levels for Early-stage Left-sided Breast Cancer

AimsTo evaluate the organ at risk (OAR) dose and its characteristic variation with different clinically usable prescription doses (RxD) for breast and chest wall radiotherapy in patients with early-stage left-sided breast cancer. Materials and methodsIn total, 145 patients with early-stage breast cancers (T1N0M0-T2N0M0) on the left side were treated with radiotherapy after a modified radical mastectomy or breast conservation surgery, with a mean age of 45.1 ± 21.6 years. The patient received 4050 cGy of field-in-field (three-dimensional conformal radiotherapy) treatment limited to the breast or chest wall, excluding the supraclavicular node, axillary node and internal mammary chain, over 15 fractions. Additional plans of 5000 cGy/25 fractions, 4500 cGy/20 fractions and 2600 cGy/5 fractions were created with no or minor changes to the original plan. Mathematical modelling was used to study the distinctive change in the dose–volume characteristics for various OARs as a function of the RxD. OAR dosages, both absolute and normalised, were expressed in terms of the RxD. The mathematical (functional) relationship between OAR doses and different prescription levels was deduced by the least squares fit method. ResultThe left lung mean dose, V5Gy (%), V10Gy (%) and V20Gy (%) and the heart mean dose, V10Gy (%) and V20Gy (%) were evaluated. The dose–volume parameters showed a parabolic variation (x2) with the RxD. Prescription normalised OAR doses showed a linear relationship with the RxD; relative dose increased with diminishing RxD. Normalised lung and heart mean doses exhibited saturation (linear relationship) with RxD variation. Paired sample t-test results between RxD versus all evaluated parameters were found to be statistically significant (P = 0.004). The Pearson correlation coefficient between different prescription levels for left lung mean dose (range 0.942–1.0), heart mean dose (range 1.0–1.0), left lung V5Gy (%) (range 0.987–1.0), left lung V10Gy (%) (range 0.991–0.999), heart V10Gy (%) (range 0.998–1.0). ConclusionThe functional form of absolute OAR dose–volume parameters versus RxD is parabolic and the RxD normalised OAR dose–volume parameter versus RxD is a straight line with a negative slope as RxD increases. This indicates an increase in the relative OAR dose–volume parameters if the RxD is reduced. This study is the first of its kind to compare the OAR doses as a function of clinically used degenerate prescription levels. These data will help to comprehend the OAR doses while adopting a new dose fractionation regimen and reviewing the radiotherapy treatment plans.

Detección de la infiltración de la cadena mamaria interna en pacientes con cáncer de mama mediante PET/RM con 18F-FDG y sus implicaciones terapéuticas

ObjectiveTo 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. MethodsProspective 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. ResultsIMCI 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%). ConclusionOur 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.

Feasibility study of adaptive radiotherapy with Ethos for breast cancer.

The aim of this study was to assess the feasibility of online adaptive radiotherapy with Ethos for breast cancer. This retrospective study included 20 breast cancer patients previously treated with TrueBeam. All had undergone breast surgery for different indications (right/left, lumpectomy/mastectomy) and were evenly divided between these four cases, with five extended cone beam computed tomography (CBCT) scans per patient. The dataset was used in an Ethos emulator to test the full adaptive workflow. The contours generated by artificial intelligence (AI) for the influencers (left and right breasts and lungs, heart) and elastic or rigid propagation for the target volumes (internal mammary chain (IMC) and clavicular lymph nodes (CLNs)) were compared to the initial contours delineated by the physician using two metrics: Dice similarity coefficient (DICE) and Hausdorff 95% distance (HD95). The repeatability of influencer generation was investigated. The times taken by the emulator to generate contours, optimize plans, and calculate doses were recorded. The quality of the scheduled and adapted plans generated by Ethos was assessed using planning target volume (PTV) coverage, homogeneity indices (HIs), and doses to organs at risk (OARs) via dose-volume histogram (DVH) metrics. Quality assurance (QA) of the treatment plans was performed using an independent portal dosimetry tool (EpiQA) and gamma index. On average, the DICE for the influencers was greater than 0.9. Contours resulting from rigid propagation had a higher DICE and a lower HD95 than those resulting from elastic deformation but remained below the values obtained for the influencers: DICE values were 0.79 ± 0.11 and 0.46 ± 0.17 for the CLN and IMC, respectively. Regarding the repeatability of the influencer segmentation, the DICE was close to 1, and the mean HD95 was strictly less than 0.15mm. The mean time was 73 ± 4 s for contour generation per AI and 80 ± 9 s for propagations. The average time was 53 ± 3 s for dose calculation and 125 ± 9 s for plan optimization. A dosimetric comparison of scheduled and adapted plans showed a significant difference in PTV coverage: dose received by 95% of the volume (D95%) values were higher and closer to the prescribed doses for adapted plans. Doses to organs at risk were similar. The average gamma index for quality assurance of adapted plans was 99.93 ± 0.38 for a 3%/3mm criterion. This study comprehensively evaluated the Ethos® adaptive workflow for breast cancer and its potential technical limitations. Although the results demonstrated the high accuracy of AI segmentation and the superiority of adapted plans in terms of target volume coverage, a medical assessment is still required.

Radiotherapy to regional nodes in early breast cancer: an individual patient data meta-analysis of 14 324 women in 16 trials

Radiotherapy has become much better targeted since the 1980s, improving both safety and efficacy. In breast cancer, radiotherapy to regional lymph nodes aims to reduce risks of recurrence and death. Its effects have been studied in randomised trials, some before the 1980s and some after. We aimed to assess the effects of regional node radiotherapy in these two eras. In this meta-analysis of individual patient data, we sought data from all randomised trials of regional lymph node radiotherapy versus no regional lymph node radiotherapy in women with early breast cancer (including one study that irradiated lymph nodes only if the cancer was right-sided). Trials were identified through the EBCTCG's regular systematic searches of databases including MEDLINE, Embase, the Cochrane Library, and meeting abstracts. Trials were eligible if they began before Jan 1, 2009. The only systematic difference between treatment groups was in regional node radiotherapy (to the internal mammary chain, supraclavicular fossa, or axilla, or any combinations of these). Primary outcomes were recurrence at any site, breast cancer mortality, non-breast-cancer mortality, and all-cause mortality. Data were supplied by trialists and standardised into a format suitable for analysis. A summary of the formatted data was returned to trialists for verification. Log-rank analyses yielded first-event rate ratios (RRs) and confidence intervals. We found 17 eligible trials, 16 of which had available data (for 14 324 participants), and one of which (henceforth excluded), had unavailable data (for 165 participants). In the eight newer trials (12 167 patients), which started during 1989-2008, regional node radiotherapy significantly reduced recurrence (rate ratio 0·88, 95% CI 0·81-0·95; p=0·0008). The main effect was on distant recurrence as few regional node recurrences were reported. Radiotherapy significantly reduced breast cancer mortality (RR 0·87, 95% CI 0·80-0·94; p=0·0010), with no significant effect on non-breast-cancer mortality (0·97, 0·84-1·11; p=0·63), leading to significantly reduced all-cause mortality (0·90, 0·84-0·96; p=0·0022). In an illustrative calculation, estimated absolute reductions in 15-year breast cancer mortality were 1·6% for women with no positive axillary nodes, 2·7% for those with one to three positive axillary nodes, and 4·5% for those with four or more positive axillary nodes. In the eight older trials (2157 patients), which started during 1961-78, regional node radiotherapy had little effect on breast cancer mortality (RR 1·04, 95% CI 0·91-1·20; p=0·55), but significantly increased non-breast-cancer mortality (1·42, 1·18-1·71; p=0·00023), with risk mainly after year 20, and all-cause mortality (1·17, 1·04-1·31; p=0·0067). Regional node radiotherapy significantly reduced breast cancer mortality and all-cause mortality in trials done after the 1980s, but not in older trials. These contrasting findings could reflect radiotherapy improvements since the 1980s. Cancer Research UK, Medical Research Council.

Detection of internal mammary chain infiltration in breast cancer patients by [18F]FDG PET/MRI. Therapy implications

ObjectiveTo 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. MethodsProspective 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. ResultsIMCI 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%). ConclusionOur 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.

Impact of Neoadjuvant Concurrent Chemoradiation (NACCRT) on Operability and Survival in Locally Advanced Inoperable Breast Cancer

Inoperable locally advanced breast cancers (LABC) are treated with neoadjuvant chemotherapy (NACT). However, many patients remain inoperable after NACT due to an inadequate response. We, therefore, investigated the role of neoadjuvant concurrent chemoradiation (NACCRT) in this setting. Patients with inoperable Stage III LABC were prospectively recruited in the study between May 2017 and December 2021. NACT consisted of 4 cycles of q3weekly Adriamycin (60 mg/m2) and Cyclophosphamide (600mg/m2), and 4 cycles of q3weekly Paclitaxel (175 mg/m2). Concurrent radiotherapy with 6 MV X-rays was given using a 3D conformal technique to a total dose of 46 Gy (2 Gy/fraction, 5 days/week) to the involved breast, axilla, supraclavicular fossa, and internal mammary chain (upper 3 intercostal spaces) along with the first two cycles of paclitaxel. A 0.5 cm bolus was used to boost the skin till the appearance of hyperpigmentation. All patients were assessed for surgery after the completion of the planned neoadjuvant treatment. Adjuvant treatments were given based on the receptor status. The impact of neoadjuvant CTRT on the pathological complete response (pCR), operability, and survival was analyzed. Event-free survival (EFS) and Overall Survival (OS) were analyzed using the Kaplan-Meier method. The study enrolled 202 female patients with a median age of 52 years, with 23.7% having IIIA, 65.3% IIIB, and 10.8% having IIIC disease. Hormone-receptor (HR) positive disease was observed in 90/202 (44.6%) patients, triple-negative (TNBC) in 50/202 (24.8%) and Her2/neu positive in 62/202 (30.7%) patients. Modified radical mastectomy was performed in 88.1% of patients, with 8.5% remaining inoperable and 3.4% declining surgery due to clinical complete response (cCR). Among the patients who underwent MRM, 65/178 (32.2%) patients had a pCR. pCR was observed in 13/81 (16%) with HR-positive disease, 21/46 (45.6%) with TNBC, and 31/51 (60.7%) patients with Her2/neu-positive disease. Grade 3 skin reactions were observed in 39/202 (19.3%). Postoperative wound morbidity requiring hospitalization was observed in 19/178 (10.6%) patients. The median follow-up was 42 months, with 4-year EFS and OS of 63.8% and 71.5%, respectively. Six out of 7 patients who were in cCR and declined surgery are alive and remain in cCR. On subgroup analysis of Her 2 positive patients, pCR was significantly associated with improved EFS and OS (89.8% vs 33.3%, p = 0.001 and 89.1% vs 44.4%, p = 0.001 respectively). Our study demonstrates the feasibility and efficacy of NACCRT in improving operability, pCR rates and survival outcomes in patients with inoperable LABC. The results suggest that NACCRT can be considered for use in clinical practice with careful patient selection. These findings contribute to the ongoing efforts to optimize treatment for this patient population and warrant further investigation in larger, randomized trials.

Association of Left Anterior Descending Coronary Artery Calcium Progression and Radiation Dose with Major Adverse Cardiac Events in Breast Cancer

Coronary artery calcium (CAC) is associated with increased risk of major adverse cardiac events (MACE). Accelerated CAC progression has been observed in patients with breast cancer after radiotherapy (RT) and there is a relationship between left anterior descending (LAD) coronary artery RT dose and the risk of coronary events. However, there is lack of consensus on LAD dose constraints for breast RT and limited data on the extent and impact of CAC progression. Our objective was to evaluate the association of LAD dose exposure and CAC progression with the risk of MACE in patients with breast cancer following RT. Retrospective analysis of 181 patients with breast cancer treated with RT between 2008 and 2019. CAC was manually measured on RT planning and follow-up CTs (with at least one-year interval) using the Agatston method. Coronary arteries were segmented using a deep learning-based automated algorithm and dosimetric parameters collected. MACE cumulative incidence was estimated, and Fine and Gray regressions performed, accounting for non-cardiac death as a competing risk. The median follow-up following RT was 70 months (interquartile range [IQR], 53-86). The median age was 63 years (IQR, 53-72), 43% had hypertension, 40% hyperlipidemia, 8% coronary heart disease (CHD). Most had pathologic stage I-II disease (76%). RT was targeted to breast/chest wall only in 60% and included regional nodes in 40% (internal mammary chain in 4%). The most common dose/fractionation was 48-50.4 Gy/25-28 fractions (67%) and 42.6-42.7 Gy/16 fractions (30%). At the time of RT, 68 (38%) had at least moderate CAC burden (CAC >100; statin-therapy indicated), but only 29 (43%) were on statin therapy. At a median interval of 44 months (IQR, 26-63), 55% (n = 84) had CAC progression, with a median increase of 52%/year (IQR, 18-193). The median time to MACE was 68 months (IQR, 53-85), with a 5-year cumulative incidence of 7.3% (15 MACE overall). Accounting for age and CHD, there was an increased risk of MACE with LAD CAC progression (subdistribution hazard ratio [SHR] 1.02/10 CAC points; 95% confidence interval [CI] 1.01 = 1.03; p = .007) and the volume of LAD receiving 15 Gy (LAD V15 Gy; SHR 1.03/%; 95% CI, 1.01-1.06; p = .004). There was no association between mean heart dose, chemotherapy, or Her2 therapy exposure and MACE (p>.05). LAD CAC progression and LAD V15 Gy dose exposure were associated with an increased risk of MACE following RT. Accelerated CAC progression was commonly observed, however most patients were under-optimized for cardiovascular (CV) risk, with less than half of statin-eligible patients with at least moderate CAC burden on statin therapy. Together, these data support more aggressive cardiac risk mitigation approaches, including guidelines-based CV risk factor modification and optimized sparing of LAD radiation dose.

Variation in Left Anterior Descending Coronary Artery Accumulated Dose Estimates during Breast Cancer Radiotherapy

Left anterior descending (LAD) coronary artery RT dose has been associated with the risk of coronary ischemic events in patients with breast cancer treated with radiotherapy (RT). However, consensus dose constraints commonly utilize mean heart dose, which has been shown to be an inadequate surrogate for LAD dose. Given the LAD is adjacent to the steep dose gradients of the left breast/chest wall, we hypothesize that variations in patient positioning or depth of breath hold may contribute to significant deviations in daily LAD dose exposure compared to predicted. Our objective was to investigate variations in accumulated LAD dose in patients with left-sided breast cancer treated with RT. Retrospective analysis of 10 consecutive patients with left-sided breast cancer treated between 2019-2022 with volumetric modulated arc therapy (VMAT) in the supine position. RT was delivered using daily cone beam computed tomography (CBCT) image guidance with deep-inspiratory breath hold technique and an optical surface monitoring system. Daily CBCT scans were individually registered to each planning CT based on daily positional changes. The LAD was manually segmented and transformed to each CBCT. Daily fractional dose was calculated (mean, volume receiving 15 Gy [V15 Gy], V30 Gy, and max) and summed to produce an accumulated dose which was compared to the predicted dose. Significant deviations in accumulated dose were defined as at least ±15% from predicted. The RT targets included breast/chest wall only (n = 1), supraclavicular nodes (n = 8), and/or internal mammary chain (n = 5). All plans were prescribed to 50 Gy in 25 fractions. The median predicted mean heart dose was 5.1 Gy. Overall, there were no significant differences between the median predicted vs. accumulated LAD doses: mean 10.4 vs. 10.2 Gy, V15 Gy 21% vs. 25%, V30 Gy 0% vs. 1%, max 24.5 vs 25.7 Gy (all p>.05). However, there was a subset of patients (n = 5, 50%) with significant deviations in accumulated vs. predicted dose (at least ±15%). For LAD mean, n = 2 had higher accumulated vs. predicted doses (16.6 vs. 11.6 Gy; 14.6 vs. 12.8 Gy), while n = 3 had lower (21.8 vs. 26.5 Gy; 2.7 vs. 4.2 Gy; 13.9 vs. 16.5 Gy). For LAD V15 Gy, n = 3 had higher accumulated vs. predicted doses (43 vs. 35%; 51% vs. 25%; 14% vs. 9%), while n = 2 had lower (49% vs. 61%; 37% vs. 56%). For LAD V30 Gy, n = 4 had higher accumulated vs. predicted doses (12% vs. 5%; 5% vs. 0%; 4% vs. 0%; 4% vs. 2%), while n = 1 had lower (32% vs. 44%). Daily setup differences, including the extent of inspiratory breath hold, may contribute to deviations in accumulated LAD dose (more than 15% of predicted) in approximately half of patients and were more pronounced in V15 and V30 Gy metrics. The potential for significant LAD dose uncertainty in a clinically meaningful subset of patients should be recognized and warrants further analysis in an expanded cohort.

Dose-Volume Predictors for Radiation Esophagitis in Breast Cancer Patients Undergoing Hypofractionated Regional Nodal Radiotherapy

Radiation esophagitis (RE) is often overlooked in breast cancer radiotherapy. This study aimed to assess the incidence and dose-volume predictors of RE in breast cancer patients undergoing hypofractionated regional nodal irradiation (RNI). Eligible patients were included who received intensity-modulated radiotherapy (RT) at the chest wall, the supraclavicular/infraclavicular fossa, level II axilla, and/or the internal mammary chain after mastectomy. The prescribed dose was 43.5 Gy in 15 fractions. The dose constraint for the esophagus was maximum dose <48 Gy. RE was evaluated weekly during RT and at 1 and 2 weeks, followed by 3 and 6 months after RT, and was graded according to the Common Toxicity Criteria for Adverse Events v3.0. The esophagus was contoured from the lower border level of the cricoid cartilage to the lower margin of the aortic arch. Esophageal total volume, mean dose (Dmean), maximum dose (Dmax), and the relative and absolute volumes receiving at least 5-45 Gy by 5 Gy increments (RV5-RV45 and AV5-AV45) were evaluated. Univariable and multivariable logistics regression analyses were performed to determine risk factors for RE, and receiver operating characteristic curves were obtained to identify the thresholds of esophageal dosimetric parameters. In total, 298 patients were included between May 8, 2020 and January 5, 2022 (minimum post-RT follow-up: 6 months). A total of 153 (51.3%) patients had left-sided breast cancer and 145 (48.7%) patients received internal mammary nodal irradiation (IMNI). Grade 2 and 3 RE incidence was 40.9% (122/298) and 0.3% (1/298), respectively. No grade 4 or 5 RE was observed. All RE cases resolved within 1 month after RT, and the median duration of RE was 3 weeks (range, 1-5). Based on univariable analyses, tumor laterality (p < .001), IMNI (p = .056) and esophageal Dmean, Dmax, RV10-RV40, and AV10-AV40 were risk factors of ≥grade 2 RE. Esophageal RV10-RV40 and AV35-AV40 were significantly associated with the risk of ≥grade 2 RE after adjusting for tumor laterality and IMNI. Based on multivariable analyses, RV25 and AV35 were optimum dose-volume predictors for ≥grade 2 RE at thresholds 20% for RV25 (35.9% vs. 60.9%, p = .04) and 0.27 mL for AV35 (31.0% vs. 54.6%, p = .04). RE is common in breast cancer patients undergoing hypofractionated RNI. With the same esophageal contouring standard, maintaining the upper esophageal V25 at <20% and V35 at <0.27 mL may decrease the risk of RE and improve the quality of life of patients.

Intensity-Modulated Proton Therapy (IMPT) Offered Advantageous Dosimetry Compared to Volumetric Arc Therapy (VMAT) or Helical Tomotherapy (HT) in Patients with Synchronous Bilateral Breast Cancer

Radiotherapy of synchronous bilateral breast cancer poses some technical challenges with regards to dose coverage and sparing of organs at risk (OAR). In this study, we aimed to evaluate dosimetric characteristics of 3 different techniques, IMPT vs photon (VMAT and HT). We hypothesized that IMPT would result in lower doses to organs at risk, as compared to the other 2 techniques. A total of 10 patients with synchronous bilateral breast cancer who were treated with VMAT at our institution were retrospectively analyzed. Clinical target volume (CTV) included chest wall and regional nodes (supraclavicular fossa and internal mammary chain) and prescription dose was 40.05 Gy in 15 daily fractions. HT and IMPT plans were generated for each patient. Dose-volume statistics, including planning target volume (PTV) coverage and dose to OAR: lungs, heart, thyroid, spinal cord, brachial plexus and esophagus, were compared between modalities using a paired T-test. Mean age of patients was 61 years (43-84). Majority of the patients (80%) were ER+ PR+ and HER2-. 40% of patients underwent breast reconstruction following surgery. All 3 techniques provided adequate target volume distribution and OAR sparing. Compared to VMAT and HT plans, IMPT had better heart and lung sparing effects, resulting in lower mean and V25 Gy heart dose; mean, V20 Gy and V5 Gy lung dose (p<0.0001). There was no significant difference in VMAT and HT plans for mean heart and lung dose. VMAT plans showed significantly lower V25 Gy heart dose on average (p = 0.04). V5 Gy lung dose was slightly lower in HT compared to VMAT plans, approaching statistical significance (p = 0.08). PTV coverage was adequate for all 3 techniques. All techniques fulfilled cord, esophagus, thyroid and brachial plexus constraints. IMPT plans showed significantly better OAR sparing compared to photon techniques. All 3 techniques met OAR constraints, and resulted in adequate target volume coverage. As IMPT is significantly more costly than VMAT or HT techniques, appropriate patient selection is important to deliver treatment in the most resource-effective manner for patients who would derive the most benefit, for example those with young age or existing heart or lung comorbidities.

Impact of Post-Mastectomy Radiotherapy on Cosmesis and Quality of Life after Deep Inferior Epigastric Perforator Flap Breast Reconstruction: A Single Institution Experience

Immediate breast reconstruction (IBR) yields better cosmetic results and reduce psychological distress than delayed (DBR). Literature data showed better local cosmesis after reconstruction autologous flaps than prothesis. Our aim is to compare cosmetic results and quality of life (QoL) after PMRT delivered either after IBR or DBR with DIEP flap. We reviewed files of 99 patients (100 DIEPs) treated in our department from January 2000 to December 2019. Patients were divided into 2 groups depending on the treatment sequence: IBR (n = 22) versus DBR (n = 78) followed by PMRT. All the patients had their DIEP flap by the same surgical team. All patients had cosmetic evaluation using Harvard/RTOG cosmesis grading scale. Fifty percent (32 in IBR and 14 in DBR group) of the patients responded to the QoL evaluation using auto questionnaires and BREAST-Q to evaluate breast specific HRQoL and satisfaction. The analysis of cosmetic scores was carried out with a Chi2 test and the analysis of QoL scores with a student test. Kaplan Meier (log-rank test) is used for recurrence-free and overall survival. Median follow-up was 56 months. Median age of the patients was 48 (28-71). In terms of disease stage: T1-2 (52%), N0 (38%). 86% of the patients had chemotherapy either in neo-adjuvant (26%) or adjuvant (60%) settings. Radiation therapy (RT) delivered a total dose ranged between 45 Gy and 50 Gy using 1.8-2.5 Gy/per fraction. Supra-clavicular and internal mammary chain irradiation was performed in 67% and 33% of the patients respectively. After surgery, 15% had post-operative complications such as DIEP necrosis (n = 8) that delayed RT delivery. Among the 99 patients, 3 died from metastatic evolution and were not included in the cosmetic and QoL analyses. Local recurrence rate was slightly higher after DBR (12.5%) as compared to IBR (3.8%). Loco-regional and metastatic recurrence rates were 4.5% and 4.5% after IBR versus 1.3% and 9% after DBR (p = NS). Disease free and overall survival were 88% and 98% at 5y and 66% and 96% at 10y.Good-to-excellent results were observed in 57% in the IBR vs 67% in the DBR (p = 0.92). There was no impact of previous chemotherapy (p = 0.21), tobacco use at diagnosis (p = 0.27), diabetes (p = 0.86), RT timing (p = 0.53) and endocrine therapy administration (p = 0.67). QoL was evaluated with the BREAST-Q self-evaluation for 5 post operative items: psycho-social, physical, sexual well-being and satisfaction with breast and global cosmetic results. Out of the 99 patients, 46% had responded to the QoL evaluation. We found no statistical difference between the two groups for all the BREAST-Q evaluation items. Our center is considered expert for DIEP reconstructions since its development in end of the nineties. Our data showed no impact PMRT using conventional fractionation (with mainly 1.8 Gy/fraction) on cosmetic results, QoL, and patients' satisfaction regardless of the timing of the breast reconstruction. Additional studies are in progress with updates.

Contribución de la medicina nuclear en la cirugía de precisión en el cáncer de mama

Nuclear medicine has significantly contributed to precision surgery in breast cancer in the past decades. Radioguided surgery (RGS) has enabled sentinel node (SN) biopsy in assessing regional nodal involvement modifying the management of patients with early breast cancer. For the axilla the SN procedure has resulted in fewer complications and better quality of life when compared with axillary lymph node dissection. Originally, SN biopsy principally concerned cT1-2 tumors without evidence of axillary lymph node metastases. However, in last years SN biopsy is also being offered to patients with large or multifocal tumors, ductal carcinoma in situ, ipsilateral breast cancer relapse, and to patients receiving neoadjuvant systemic treatment (NST) for breast sparing surgery. Parallel to this evolution various scientific associations are trying to homogenise issues such as radiotracer choice, breast injection site, preoperative imaging standardisation and SN biopsy timing in relation to NST as well as management of non-axillary SN metastasis (e.g. internal mammary chain). Additionally, RGS is currently used to accomplish primary breast tumour excision either by intralesional radiocolloid injection or by radioactive iodine seed implantation which is also employed to target metastatic axillary lymph nodes. This latter procedure contributes to manage the node-positive axilla in combination with 18F-FDG PET/CT in an effort to tailor systemic and loco regional treatment.

Nuclear medicine contribution to precision surgery in breast cancer

Nuclear medicine has significantly contributed to precision surgery in breast cancer in the past decades. Radioguided surgery (RGS) has enabled sentinel node (SN) biopsy in assessing regional nodal involvement modifying the management of patients with early breast cancer. For the axilla the SN procedure has resulted in fewer complications and better quality of life when compared with axillary lymph node dissection. Originally, SN biopsy principally concerned cT 1-2 tumours without evidence of axillary lymph node metastases. However, in last years SN biopsy is also being offered to patients with large or multifocal tumours, ductal carcinoma in situ, ipsilateral breast cancer relapse, and to patients receiving neoadjuvant systemic treatment (NST) for breast sparing surgery. Parallel to this evolution various scientific associations are trying to homogenise issues such as radiotracer choice, breast injection site, preoperative imaging standardisation and SN biopsy timing in relation to NST as well as management of non-axillary SN metastasis (e.g. internal mammary chain). Additionally, RGS is currently used to accomplish primary breast tumour excision either by intralesional radiocolloid injection or by radioactive iodine seed implantation which is also employed to target metastatic axillary lymph nodes. This latter procedure contributes to manage the node-positive axilla in combination with 18F-FDG PET/CT in an effort to tailor systemic and loco regional treatment.