Locoregional Radiotherapy Research Articles

Vascularized Bone Reconstruction for Recalcitrant Clavicular Nonunion: A Systematic Review of the Literature.

Clavicular nonunion is an uncommon complication with a significant impact on quality of life and can be difficult to manage. In recalcitrant cases, or situations unfavorable for take of nonvascularized grafts, vascularized osseous reconstruction may be utilized. Several donor sites for such flaps have been described, with each associated with unique benefits and drawbacks. A systematic review utilizing MEDLINE and Embase databases was performed for cases of vascularized bone reconstruction for clavicle nonunion. Twenty-six papers met inclusion, comprising 67 patients. Mean age was 43.1 years, across 32 male and 35 female patients. Mean period of nonunion was 43.2 months in the fibular group, 42.0 months in the medial femoral condyle (MFC), and 12 months in the rib flap group.Patients had undergone a mean of 2.67 prior operations at the time of vascularized osseous flap; a proportion of patients had undergone prior locoregional radiotherapy (9/26) or been complicated by infection (12/22). Radiological union was achieved in 95.2% (20/21) of fibular flaps, 95.6% (25/27) of MFC flaps, and 66.7% (2/3) of rib flaps. Mean time to union was 10.6 months for the fibular group, 7.8 months for the MFCs, and 4.0 months for the rib flaps. Complications occurred in 55.6% (20/36) of patients having fibular flaps, 26.1% (6/23) of MFC flaps, and 50% (2/4) of rib flaps. All osseous flaps yielded similar and consistent rates of union when used to reconstruct defects of the clavicle. Higher complication rates, particularly donor site morbidity, were noted with fibula and rib flaps when compared to the MFC.Level of evidence 3a.

Case report: Efficacy of later-line fam-trastuzumab deruxtecan in a patient with triple-positive breast cancer with brain metastases

Fam-trastuzumab deruxtecan (T-DXd) has demonstrated substantial antitumor activity and durable responses in patients with human epidermal growth factor receptor 2 positive (HER2+) metastatic breast cancer. We report here the treatment outcomes of T-DXd in a patient with HER2+ breast cancer with brain metastases that repeatedly recurred and progressed after two lines of salvage therapy. In 2016, a 23-year-old G0P0 female with risk factors including menarche at age 9 years, Li-Fraumeni syndrome, and a strong family history of cancer was diagnosed with bilateral, triple-positive breast cancer. She received chemotherapy, HER2-targeted therapies, total mastectomy, and locoregional radiotherapy, but a brain metastasis in the left parieto-occipital lobe was detected in 2020. After receiving capecitabine, lapatinib, gonadotropin-releasing hormone (GnRH) agonist, and tamoxifen, multiple new lesions appeared in the brain after 14 months. The patient then received capecitabine, neratinib, GnRH agonist, and letrozole; however, her brain metastases still progressed after 7 months. In 2022, she started T-DXd treatment. Good response to treatment was observed 4 months later, including a continuous decrease in the cancer antigen 15-3 level, a reduction in the size of the major brain tumor, and the absence of new lesions. Now aged 30, the patient is continuing to receive T-DXd treatment to prevent recurrence. We conclude that T-DXd was effective for the treatment of brain metastases in this young patient with triple-positive metastatic breast cancer who had multiple risk factors and had received several anti-HER2 therapies prior to T-DXd.

Whether Primary Bone-Only Oligometastatic Nasopharyngeal Carcinoma Patients Benefit From Radiotherapy to the Bones on the Basis of Palliative Chemotherapy Plus Locoregional Radiotherapy?-A Large-Cohort Retrospective Study.

Whether to perform local radiotherapy on metastatic bone for primary bone-only oligometastatic nasopharyngeal carcinoma (NPC) patients remains unclear. Therefore, we analyzed the treatment methods and their survival and developed a prognostic model to predict outcomes and guide personalized treatment. We studied 308 primary bone-only oligometastatic NPC patients who were treated with either palliative chemotherapy (PCT) alone, PCT combined with locoregional radiotherapy (LRRT), or PCT, LRRT, and radiotherapy to metastatic bones (bRT). The primary endpoint was overall survival (OS). Cox regression was utilized to identify independent prognostic factors, leading to the construction of a nomogram model. Patients were stratified into two risk groups based on median prognostic scores, and treatment modalities were compared using log-rank test while employing the inverse probability of treatment weighting (IPTW) to balance baseline characteristics and adjust for sample size differences between risk groups. The best OS was observed in the group treated with PCT, LRRT, and bRT (HR = 0.60, 95% CI: 0.45-0.81, p = 0.002). Multivariable analysis revealed that age, N stage, pre-treatment levels of LDH, and EBV DNA were independent prognostic factors for OS. In total, 155 patients were in low-risk group while 153 were in high-risk group. Before and after IPTW, the high-risk group benefited from the PCT, LRRT, and bRT regimen (adjusted HR = 0.53, 95% CI: 0.42-0.67, p < 0.001; unadjusted HR = 0.59, 95% CI: 0.42-0.83, p = 0.007), while the low-risk group did not (adjusted HR = 0.79, 95% CI: 0.56-1.11, p = 0.345; unadjusted HR = 0.65, 95% CI: 0.37-1.14, p = 0.309). Best outcomes of the whole cohort were seen with PCT + LRRT + bRT. Our study identified age, N stage, pre-treatment LDH levels, and EBV DNA levels as independent prognostic factors for OS. The high-risk group demonstrated a longer OS when treated with PCT + LRRT + bRT, whereas the low-risk group did not benefit from the combinatorial treatment.

Immune checkpoint inhibitors for patients with metastatic triple-negative inflammatory breast cancer (INCORPORATE): An international cohort study

BackgroundInflammatory breast cancer (IBC) is the most aggressive clinical presentation of breast cancer, recapitulating a specific biology with more immune-vulnerability than non-IBC. Patients with metastatic, triple-negative IBC (mTN-IBC) receive immune checkpoint inhibitors (ICIs) and chemotherapy, similarly to patients with triple-negative non-IBC. However, the benefit derived from ICI incorporation in this rare type of breast cancer is unknown. MethodsWe conducted a multicenter, international, retrospective, cohort study to evaluate the activity of ICIs in patients with metastatic, triple-negative, primary IBC, who received ICIs plus first line chemotherapy from January 2015 to April 2023. A sample size of 42 patients allowed to detect an increase in 6-months real-world progression-free survival (rwPFS) rate from 40 % with only chemotherapy to 60 % with ICI and chemotherapy. Results41 patients from eight international IBC referral centers were included (61 % with primary, de novo mTN-IBC, 61 % with visceral disease). All received ICIs plus first line chemotherapy and 24 % underwent breast surgery and/or locoregional radiotherapy. After a median follow-up of 19.3 months, the 6-months rwPFS rate was 30 % (95 % Confidence Interval [CI], 17–45 %), the median rwPFS was 3.3 months (95 % CI: 2.2–5.4), the median overall survival was 15.7 months (95 % CI: 6.8–16.3). ConclusionsThis one-sample analysis showed a poor outcome of patients with mTN-IBC, despite the treatment with ICI, in contrast with the expected benefit based on preclinical evidence of immune-vulnerability of IBC. These results suggest the need to further investigate the role of immunotherapy in this aggressive and rare type of breast cancer presentation.

Automated dose evaluation on daily cone-beam computed tomography for breast cancer patients

Background and purposeOur goal was to develop a workflow to automatically evaluate delivered dose on daily cone beam computed tomography (CBCT) in all breast cancer patients to assess dosimetric impact of anatomical changes and guide decision-making for offline plan adaptation. Materials and methodsThe workflow automatically processes the daily CBCTs of all breast cancer patients receiving local and locoregional radiotherapy. The planning-CT is registered to the CBCT to create a synthetic CT and propagate contours. A forward dose calculation is performed, and DVH parameters are extracted and printed in a report. We evaluated the workflow on a group level and in a subset of 30 patients on a patient-specific level, including comparison to clinical evaluation on additional planning-CT in 10 patients. Results7454 fractions in 647 patients were analyzed over a period of seven months. Median breast clinical target volume V95% was ≥ 95 % for 97 % of the patients. The workflow would have provided useful additional insights for decision-making for the requirement of plan adaptation, based on debatable disagreement with the clinical decision in half of the cases with an additional planning-CT. The workflow also identified cases with suboptimal coverage not identified in the clinical procedure. ConclusionWe developed a fully automated workflow for dose evaluation on daily CBCT for local and locoregional breast radiotherapy. We have demonstrated its potential for aiding decision-making for plan adaptation in patients with changing anatomy and its capability to highlight patients that may receive suboptimal treatment and require closer clinical evaluation of treatment quality.

Impact of Radiation Therapy on Serum Humanin and MOTS-c Levels in Patients with Lung or Breast Cancer.

Lung and breast cancer are the most frequent causes of death from cancer globally. The objectives of this research were to evaluate the serum mitochondrial open reading frame of the 12S rRNA-c (MOTS-c) and humanin levels in lung or breast cancer patients, and investigate the impacts of radiation therapy on the circulating levels of these peptides. 35 lung cancer patients, 34 breast cancer patients, and healthy volunteers as a control group were recruited in this prospective observatory research. Lung cancer patients with stage IIIA/IIIB were treated with paclitaxel-based chemotherapy plus radiotherapy (2 Gy per day, 30 times, 60 Gy total dose). Breast cancer stage IIA/IIB patients were treated with postoperative locoregional radiation therapy (2 Gy per day, 25 times, 50 Gy total dose). The ELISA method was used to detect serum humanin and MOTS-c levels during, before, and after radiotherapy. We observed marked elevations in circulating MOTS-c, but not humanin levels in patients with lung cancer (P < 0.001). Radiation therapy led to a marked augmentation in MOTS-c levels in these patients (P < 0.001). On the other hand, there was a marked decline in humanin, but not MOTS-c, levels in breast cancer patients (P < 0.001). Our research has shown, for the first time, that increased MOTS-c and decreased humanin levels play a role in lung cancer and breast cancer, respectively. Additionally, radiotherapy modifies MOTS-c levels in patients with lung, but not breast cancer.

How Effective is Deep Inspiration Breath Hold in Minimizing Cardiac Doses During Hybrid Radiotherapy Treatment for Left-Sided Breast Cancer with Comprehensive Regional Nodes?

In the context of left breast cancer radiotherapy, long term cardiopulmonary toxicity has been well-documented, significant efforts have been undertaken to mitigate such toxicity by using 4D gating, deep inspiration breath-hold(DIBH) and active breath control(ABC) techniques. To evaluate and compare the cardio-pulmonary radiation doses incurred during postmastectomy radiotherapy (PMRT) in two distinct breathing conditions such as DIBH and Free Breathing (FB), with a specific focus on the left chest wall with comprehensive regional nodal irradiation. A prospective dosimetric study was conducted on 15 patients who received adjuvant loco-regional radiotherapy of chest-wall (CW), supraclavicular fossa(SCF), and internal mammary region(IMC), with or without axilla. Two sets of planning CT scans were taken in DIBH and FB conditions. The dosimetric difference between DIBH CT and FB CT plans analyzed using Wilcoxon signed-rank test, employing SPSS software version 21.0. Comparison of DIBH and FB parameters for target coverage revealed a statistically significant advantage with DIBH in SCF(D95, V90, p<0.017) and IMC(D98, V90 & V95, p<0.03). Dosimetric characteristics of heart and LAD exhibited statistically significant lower doses with DIBH (V20, V25, and Dmean, p<0.001) compared to FB plans. Lung doses were similar with no discernible advantage of one technique over the other. Other OARs such as contralateral breast (p=0.027) and esophagus (p=0.001) received lower doses with the DIBH technique while the spinal cord (p=0.691) and thyroid(p=0.496) showed no significant difference. Maximum heart distance (p= 0.001), central lung distance (p= 0.011) and Haller index (p= 0.001) exhibited statistical significance between the two techniques, whereas chest wall separation showed no significant statistical difference (p=0.629). DIBH demonstrates a substantial reduction in cardiac and LAD doses compared to the FB technique. This study underscores the efficacy of DIBH as a viable strategy for mitigating cardiac and LAD radiation doses in left-sided breast cancer patients undergoing PMRT of chest wall with comprehensive regional nodes.

Toxicity and quality of life after locoregional radiotherapy in patients with thyroid cancer

Toxicity and quality of life after locoregional radiotherapy in patients with thyroid cancer

Combination of locoregional radiotherapy with a TIM-3 aptamer improves survival in diffuse midline glioma models.

Pediatric diffuse midline gliomas (DMG) with altered H3-K27M are aggressive brain tumors that arise during childhood. Despite advances in genomic knowledge and the significant number of clinical trials testing new targeted therapies, patient outcomes are still poor. Immune checkpoint blockades with small molecules, such as aptamers, are opening new therapeutic options that represent hope for this orphan disease. Here, we demonstrated that a TIM-3 aptamer (TIM-3 Apt) as monotherapy increased the immune infiltration and elicited a strong specific immune response with a tendency to improve the overall survival of treated DMG-bearing mice. Importantly, combining TIM-3 Apt with radiotherapy increased the overall median survival and led to long-term survivor mice in 2 pediatric DMG orthotopic murine models. Interestingly, TIM-3 Apt administration increased the number of myeloid populations and the proinflammatory CD8-to-Tregs ratios in the tumor microenvironment as compared with nontreated groups after radiotherapy. Importantly, the depletion of T cells led to a major loss of the therapeutic effect achieved by the combination. This work uncovers TIM-3 targeting as an immunotherapy approach to improve the radiotherapy outcome in DMGs and offers a strong foundation for propelling a phase I clinical trial using radiotherapy and TIM-3 blockade combination as a treatment for these tumors.

Postoperative radiotherapy in women with early operable breast cancer (Scottish Breast Conservation Trial): 30-year update of a randomised, controlled, phase 3 trial

Breast-conserving surgery, adjuvant systemic therapy, and radiotherapy are the standard of care for most women with early breast cancer. There are few reports of clinical outcomes beyond the first decade of follow-up of randomised trials comparing breast-conserving surgery with or without radiotherapy. We present a 30-year update of the Scottish Breast Conservation Trial. In this randomised, controlled, phase 3 trial across 14 hospitals in Scotland, women aged younger than 70 years with early breast cancer (tumours ≤4 cm [T1 or T2 and N0 or N1]) were included. They underwent breast-conserving surgery (1 cm margin) with axillary node sampling or clearance. Oestrogen receptor (ER)-rich patients (≥20 fmol/mg protein) received 20 mg oral tamoxifen daily for 5 years. ER-poor patients (<20 fmol/mg protein) received chemotherapy (cyclophosphamide 600 mg/m2, methotrexate 50 mg/m2, and fluorouracil 600 mg/m2 every 21 days intravenously in eight courses). Stratification was by menstrual status (within or more than 12 months from last menstrual period) and ER status (oestrogen concentration ≥20 fmol/mg protein, <20 fmol/mg protein, or unknown) and patients were randomly assigned (1:1) to high-dose (50 Gy in 20-25 fractions) local or locoregional radiotherapy versus no radiotherapy. No blinding was possible due to the nature of the treatment. We report the primary endpoint of the original trial, ipsilateral breast tumour recurrence, and the co-primary endpoint, overall survival. Clinical outcomes were compared by the log-rank test. Hazard ratios (HRs) are reported, with no radiotherapy as the reference group. Failures of the proportional hazards assumption are reported if significant. All analyses are by intention to treat. Between April 1, 1985, and Oct 2, 1991, 589 patients were enrolled and randomly assigned to the two treatment groups (293 to radiotherapy and 296 to no radiotherapy). After exclusion of four ineligible patients (two in each group), there were 291 patients in the radiotherapy group and 294 patients in the no radiotherapy group. Median follow-up was 17·5 years (IQR 8·4-27·9). Ipsilateral breast tumour recurrence was significantly lower in the radiotherapy group than in the no radiotherapy group (46 [16%] of 291 vs 107 [36%] of 294; HR 0·39 [95% CI 0·28-0·55], p<0·0001). Although there were differences in the hazard rate for ipsilateral breast tumour recurrence in the first decade after treatment (HR 0·24 [95% CI 0·15-0·38], p<0·0001), subsequent risks of ipsilateral breast tumour recurrence were similar in both groups (0·98 [0·54-1·79], p=0·95). There was no difference in overall survival between the two groups (median 18·7 years [95% CI 16·5-21·5] in the no radiotherapy group vs 19·2 years [16·9-21·3] in the radiotherapy group; HR 1·08 [95% CI 0·89-1 ·30], log-rank p=0·43). Our findings suggest that patients whose biology predicts a late relapse a decade or more after breast-conserving surgery for early breast cancer might gain little from adjuvant radiotherapy. Breast Cancer Institute (part of Edinburgh and Lothian Health Foundation) and PFS Genomics (now part of Exact Sciences).

Chemotherapy for post-menopausal women with early breast cancer seems not to result in clinically significant changes in thyroid function.

Adjuvant chemotherapy is often indicated in patients diagnosed with early breast cancer (EBC). Among others, weight gain is one of the observed side effects of both chemotherapy and other cancer treatments; however, the mechanism is not well-described. In this study, we aimed to assess thyroid function before and shortly after the course of chemotherapy for EBC. This is a prospective cohort study of women diagnosed with EBC. The main outcome was the thyroid function and body weight before and after completing chemotherapy. Secondary outcomes were the presence of thyroid autoantibodies and treatment radiation dosage. We included 72 patients treated with adjuvant chemotherapy, whereas 59 patients also received supraclavicular locoregional radiotherapy. Triple-negative breast cancer (BC) patients receiving chemoimmunotherapy were excluded. After the chemotherapy, we observed an increase in thyroid-stimulating hormone (p = 0.03) and a decrease in free-thyroxine (p = 0.0006), with no significant weight change. The prevalence of autoimmune thyroiditis was low. On average 3 months post-chemo, we found no statistically significant difference in the thyroid function of women treated versus not treated with supraclavicular locoregional radiotherapy. Although statistically significant changes in thyroid hormones were observed, this study suggests no obvious clinically significant changes in thyroid function in women with early BC after the course of chemotherapy. The decrease in thyroid function was not related to autoimmunity, non-thyroidal illness, radiotherapy, or high-dose corticosteroids. Further studies with a longer follow-up of thyroid function after adjuvant chemotherapy and supraclavicular locoregional radiotherapy are needed.

Quality of Life Outcomes in Breast Cancer Patients Receiving Chemotherapy With or Without Radiation Therapy

PurposeUnderstanding quality of life (QOL) implications of individual components of breast cancer treatment is important as systemic therapies continue to improve oncologic outcomes. We hypothesized that adjuvant radiation therapy does not significantly impact QOL domains in breast cancer patients undergoing chemotherapy. MethodsData was drawn from three prospective studies in women with localized breast cancer being treated with chemotherapy from March 2014 to December 2019. Patient-reported measures were collected at baseline (pretreatment) and post-treatment using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) measure, which consists of 5 subscales. Changes in mean QOL scores in patients who received radiotherapy were compared to those who did not using a one-sided noninferiority method. Statistical significance was determined below 0.05 to meet noninferiority. ResultsIn a sample of 175 patients, 131 were treated with radiation and 44 had no radiation. The sample consisted mostly of stage I-II breast cancer (78%) with hormone receptor positive (59%) disease, receiving either neoadjuvant (36%) or adjuvant chemotherapy (64%). Mean change in QOL for the group treated with radiation compared to no radiation was noninferior with respect to Physical Well-Being (P = .0027), Social/Family Well-Being (P = .0002), Emotional Well-Being (P = .0203), FACIT-Fatigue Subscale (P = .0072), and the Total FACIT-F score (P = .0005); however, mean change in QOL did not meet noninferiority for Functional Well-Being (P = .0594). ConclusionPatient-reported QOL from baseline to post-treatment, using the Total FACIT-F score, was noninferior in patients treated with versus without radiation therapy. This finding, in addition to individualized QOL subscales, provides important information in the informed decision-making process when discussing the effects of locoregional radiation on QOL in localized breast cancer patients treated with chemotherapy.

Proton therapy reduces the effective dose to immune cells in breast cancer patients.

The effective dose to circulating immune cells (EDIC) is associated with survival in lung and esophageal cancer patients. This study aimed to evaluate the benefit of intensity-modulated proton therapy (IMPT) for EDIC reduction as compared to volumetric modulated arc therapy (VMAT) in patients with locally advanced breast cancer (BC). Ten BC patients treated with locoregional VMAT after breast-conserving surgery were included. Mean dose to the heart (MHD), lungs (MLD), and liver (MlD), as well as the integral dose to the body (ITD), were retrieved, and we calculated EDIC as 0.12 × MLD + 0.08 × MHD + 0.15 × 0.85 × √(n/45) × MlD + (0.45 + 0.35 × 0.85 × √(n/45)) × ITD/(62 × 103), where n is the number of fractions. EDIC was compared between VMAT and IMPT plans. Median EDIC was reduced from 3.37 Gy (range: 2.53-5.99) with VMAT to 2.13 Gy (1.31-3.77) with IMPT (p < 0.01). For left-sided BC patients, EDIC was reduced from 3.15 Gy (2.53-3.78) with VMAT to 1.65 Gy (1.31-3.77) with IMPT (p < 0.01). For right-sided BC patients, EDIC was reduced from 5.60 Gy (5.06-5.99) with VMAT to 3.38 Gy (3.10-3.77) with IMPT (p < 0.01). Right-sided BC patients had ahigher EDIC irrespective of the technique. Integral dose reduction was the main driver of EDIC reduction with IMPT and was associated with lung sparing for left-sided BC patients or liver sparing for right-sided BC patients. IMPT significantly reduced EDIC in BC patients undergoing locoregional adjuvant radiotherapy. Integral total dose reduction, associated with improved lung sparing in left-sided BC patients or liver sparing in right-sided BC patients, mainly drove EDIC reduction with IMPT. The emergence of dynamic models taking into account the circulatory kinetics of immune cells may improve the accuracy of the estimate of the dose received by the immune system compared to calculation of the EDIC, which is based solely on static dosimetric data.

Locoregional Radiotherapy in Patients with Advanced Breast Cancer Treated with Cyclin-Dependent Kinase 4/6 Inhibitors Based on Real-World Data.

The use of locoregional radiotherapy (RT) in patients with advanced ER-positive, HER2-negative breast cancer remains a topic of ongoing debate. In this study, we aimed to evaluate the efficacy of locoregional RT in advanced breast cancer patients treated with cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in a first-line setting. We conducted a retrospective analysis of patients diagnosed with advanced breast cancer between 2018 and 2023 who received treatment with CDK4/6i and underwent locoregional radiotherapy. Among the 371 patients treated with CDK4/6i as part of their first-line therapy, 23 received locoregional RT either concurrently or sequentially with CDK4/6 inhibitors. Disease progression within the breast occurred in 19 patients (5.1%). Among these cases, five patients had previously undergone breast RT (5/23, 21.7%), while 14 did not (14/348, 4.0%, p = 0.004). All cases of local progression after RT followed palliative doses and were accompanied by early systemic progression. The 2-year PFS in the entire cohort of patients treated with locoregional RT was 65.7% (95% CI: 40.5-82.3%). Notably, patients who received higher RT doses had longer 2-year PFS (83.3%, 95% CI: 27.3-97.5%) than those with palliative RT doses (59.3%, 95% CI: 30.7-79.3%); however, the results were not statistically significant (p = 0.58). Furthermore, the 2-year local control in the entire cohort with locoregional RT was 73.0% (95% CI: 46.5-87.9%). Importantly, no local progression was observed after RT when using high doses. The addition of locoregional radiotherapy to first-line CDK4/6 inhibitors warrants further investigation across various clinical scenarios in advanced breast cancer. Palliative radiation regimens delivered early in breast oligoprogression may not always suffice, emphasizing the need for comprehensive studies in this context.

Outcomes of De Novo Oligometastatic Breast Cancer Treated With Surgery of Primary and Metastasis Directed Radiotherapy.

With sensitive imaging for breast cancer, the question arises whether present-day oncologists treat dOMBC with palliative systemic therapy (ST), which, a few years earlier, would have been treated with curative intent. We retrospectively analyzed outcomes of dOMBC treated with curative intent using a combination of surgery, metastasis-directed radiotherapy (RT), and adjuvant/neoadjuvant ST and have also explored the possible role of total lesional glycolysis of metastases and p53 immunohistochemistry in predicting outcomes. Data were collected from a prospectively maintained database using electronic medical records and Radiation Oncology Information System. In the study, dOMBC was defined as up to 3 metastatic sites, all amenable to treatment with ablative RT and primary and axillary disease amenable to curative surgery. Patients were treated with surgery, ST, and RT. Patients underwent either breast conservation surgery or modified radical mastectomy. Patients were treated with 6 to 8 cycles of chemotherapy in the neoadjuvant and/or adjuvant setting. Hormone receptor-positive patients received either tamoxifen or aromatase inhibitors. Trastuzumab was offered to Her-2-neu receptor-positive patients. RT included locoregional RT and metastases-directed ablative body RT. The median progression-free survival was 39 months (95% CI: -28.7 to 50.1mo). Two and 3 year estimated disease-free survival (DFS) was 79% and 60.5%, respectively. The median overall survival was not reached. The estimated 3-year overall survival was 87.3%. Total lesional glycolysis of metastases score and p53 status did not affect DFS. Combination treatment of surgery, metastases-directed ablative RT, and ST may provide prolonged DFS in dOMBC.

Increased Microvascular Filtration and Vascular Endothelial Growth Factor-D associated with Changed Lymphatic Vessel Morphology in Breast Cancer Treated Patients.

Vascular endothelial growth factors (VEGF) and inflammatory cytokines are indicated to be implicated in lymphedema development. We aimed to describe changes in microvascular filtration and VEGFs in a patient cohort vulnerable to breast cancer-related lymphedema development correlated with data on lymphatic morphology and function. Consecutive node-positive breast cancer patients operated in the axilla and evaluated approximately 12 months after adjuvant locoregional radiotherapy were studied. Capillary filtration rate (CFR) and isovolumetric pressure of the arms were measured by strain gauge plethysmography, and 13 blood proteins were quantified by Luminex and Elisa technology in 28 patients and 18 healthy controls. The CFR was reduced in both arms from baseline to 1-year follow-up (ipsilateral: P = 0.016 and contralateral: P = 0.001). When stratifying lymphatic complications (morphologic abnormalities and/or breast cancer-related lymphedema), CFR reached a lower steady-state in the arms with normal morphology (I:P = 0.013 and C:P = 0.013) whereas the ipsilateral arm with lymphatic complications remained unchanged (P = 0.457). In patients with lymphatic abnormal vessels, the levels of VEGF-D were 86% higher than in patients with normal lymphatic vessels (P = 0.042), whereas levels of VEGFR-3 were 64% higher (P = 0.016). Through one year of follow-up, CFR did not decrease in the lymphatic complicated treated arms as observed in noncomplicated treated arms. The patients had increased levels of VEGF-D and VEGFR-3. This correlation suggests that VEGF plays a role in the appearance of subcutaneous abnormal lymphatic vessels in the treated arms, which also maintain a fluid filtration/drainage mismatch up to one year after breast cancer treatment.

Evaluating Danish Breast Cancer Group locoregional radiotherapy guideline adherence in clinical treatment data 2008–2016: The DBCG RT Nation study

Background and purposeGuideline adherence in radiotherapy is crucial for maintaining treatment quality and consistency, particularly in non-trial patient settings where most treatments occur. The study aimed to assess the impact of guideline changes on treatment planning practices and compare manual registry data accuracy with treatment planning data. Materials and methodsThis study utilised the DBCG RT Nation cohort, a collection of breast cancer radiotherapy data in Denmark, to evaluate adherence to guidelines from 2008 to 2016. The cohort included 7448 high-risk breast cancer patients. National guideline changes included, fractionation, introduction of respiratory gating, irradiation of the internal mammary lymph nodes, use of the simultaneous integrated boost technique and inclusion of the Left Anterior Descending coronary artery in delineation practice. Methods for structure name mapping, laterality detection, detection of temporal changes in population mean lung volume, and dose evaluation were presented and applied. Manually registered treatment characteristic data was obtained from the Danish Breast Cancer Database for comparison. ResultsThe study found immediate and consistent adherence to guideline changes across Danish radiotherapy centres. Treatment practices before guideline implementation were documented and showed a variation among centres. Discrepancies between manual registry data and actual treatment planning data were as high as 10% for some measures. ConclusionNational guideline changes could be detected in the routine treatment data, with a high degree of compliance and short implementation time. Data extracted from treatment planning data files provides a more accurate and detailed characterisation of treatments and guideline adherence than medical register data.

Comparison of the use of a clinically implemented deep learning segmentation model with the simulated study setting for breast cancer patients receiving radiotherapy.

Deep learning (DL) models for auto-segmentation in radiotherapy have been extensively studied in retrospective and pilot settings. However, these studies might not reflect the clinical setting. This study compares the use of a clinically implemented in-house trained DL segmentation model for breast cancer to a previously performed pilot study to assess possible differences in performance or acceptability. Sixty patients with whole breast radiotherapy, with or without an indication for locoregional radiotherapy were included. Structures were qualitatively scored by radiotherapy technologists and radiation oncologists. Quantitative evaluation was performed using dice-similarity coefficient (DSC), 95th percentile of Hausdorff Distance (95%HD) and surface DSC (sDSC), and time needed for generating, checking, and correcting structures was measured. Ninety-three percent of all contours in clinic were scored as clinically acceptable or usable as a starting point, comparable to 92% achieved in the pilot study. Compared to the pilot study, no significant changes in time reduction were achieved for organs at risks (OARs). For target volumes, significantly more time was needed compared to the pilot study for patients including lymph node levels 1-4, although time reduction was still 33% compared to manual segmentation. Almost all contours have better DSC and 95%HD than inter-observer variations. Only CTVn4 scored worse for both metrics, and the thyroid had a higher 95%HD value. The use of the DL model in clinical practice is comparable to the pilot study, showing high acceptability rates and time reduction.

Radiation enhancement using focussed ultrasound-stimulated microbubbles for head and neck cancer: A phase 1 clinical trial

Background and purposePreclinical research demonstrated that the exposure of microbubbles (intravascular gas microspheres) to focussed ultrasound within the targeted tumour upregulates pro-apoptotic pathways and enhances radiation-induced tumour cell death. This study aimed to assess the safety and efficacy of magnetic resonance (MR)-guided focussed ultrasound-stimulated microbubbles (MRgFUS-MB) for head and neck cancers (HN). Materials and methodsThis prospective phase 1 clinical trial included patients with newly diagnosed or recurrent HN cancer (except nasopharynx malignancies) for whom locoregional radiotherapy with radical- or palliative-intent as deemed appropriate. Patients with contraindications for microbubble administration or contrast-enhanced MR were excluded. MR-coupled focussed ultrasound sonicated intravenously administered microbubbles within the MR-guided target volume. Patients receiving 5–10 and 33–35 radiation fractions were planned for 2 and 3 MRgFUS-MB treatments, respectively. Primary endpoint was toxicity per CTCAEv5.0. Secondary endpoint was tumour response at 3 months per RECIST 1.1 criteria. ResultsTwelve patients were enrolled between Jun/2020 and Nov/2023, but 1 withdrew consent. Eleven patients were included in safety analysis. Median follow-up was 7 months (range, 0.3–38). Most patients had oropharyngeal cancer (55 %) and received 20–30 Gy/5–10 fractions (63 %). No systemic toxicity or MRgFUS-MB-related adverse events occurred. The most severe acute adverse events were radiation-related grade 3 toxicities in 6 patients (55 %; dermatitis in 3, mucositis in 1, dysphagia in 6). No radiation necrosis or grade 4/5 toxicities were reported. 8 patients were included in the 3-month tumour response assessment: 4 had partial response (50 %), 3 had complete response (37.5 %), and 1 had progressive disease (12.5 %). ConclusionsMRgFUS-MB treatment was safe and associated with high rates of tumour response at 3 months.

Oncologic outcomes of de-escalating axillary treatment in clinically node-positive breast cancer patients treated with neoadjuvant systemic therapy – A two center cohort study

BackgroundThe aim of the present study was to report the 5-year axillary recurrence-free interval (aRFI) in clinically node-positive breast cancer patients treated according to a de-escalating axillary treatment protocol after neoadjuvant systemic therapy (NST). MethodsAll patients diagnosed in two hospitals between October 2014 and March 2021 were identified retrospectively. Data on diagnostic workup, treatment and follow-up was collected. Adjuvant axillary treatment was considered based on the initial staging using 18F-FDG PET/CT and the results of axillary lymph node marking with a radioactive-iodine seed protocol or a targeted axillary dissection procedure. Follow-up was updated until 27th April 2024. Kaplan-Meier curves were calculated to report the 5-year aRFI with corresponding 95 % confident intervals (95%-CI). ResultsA total of 199 patients were included. Axillary pathological complete response was reported in 66 (33.2 %). Based on the treatment protocol and initial clinical staging, no adjuvant axillary treatment was indicated in 30 patients (15 %), while 139 (70 %) received axillary radiotherapy without performance of an axillary lymph node dissection (ALND). The remaining 30 patients (15 %) underwent an ALND with additional locoregional radiotherapy. A median follow-up of 62 months (30–106) showed that 4 (2 %) patients experienced an axillary recurrence after 7, 8, 36 and 36 months, respectively. In all 4 patients, synchronous distant metastases were diagnosed. The estimated 5-year aRFI was 97.8 % (95%-CI 95.6–99.9 %) ConclusionAlthough longer follow-up should be awaited before final conclusions can be drawn regarding the oncological safety of this approach, the implementation of a de-escalating axillary treatment protocol appears to be safe since the estimated 5-year aRFI is 97.8 %.