Including Radiation Therapy Research Articles

Neoadjuvant immunotherapy plus chemotherapy in high altitude natives with resectable esophageal squamous cell carcinoma in Tibet

Neoadjuvant therapy followed by surgery has been proved to improve the survival of patients with ESCC, and neoadjuvant chemoradiotherapy (nCRT) is the standard of care in most areas of the world. However, multimodality therapy including radiation therapy is actually limited in the current treatment of esophageal cancer in Tibet. The role of neoadjuvant immunotherapy in resectable esophageal cancer has been assessed in multiple phase II clinical trials, but there's lack of evidence of applying neoadjuvant immunotherapy plus chemotherapy in Tibetan residents. Patients with previously treatment-naïve, resectable ESCC were included in this study. The preoperative treatment regimen included Tislelizumab, nab-paclitaxel and carboplatin. Surgery was planned for every patient who completed neoadjuvant treatment. Surgical approaches and extent of esophageal resection was chosen depended on tumor location. 23 patients with resectable ESCC were included from January 2022 to May 2024 in this study. Among all patients, 5 (21.7%) had thyroid nodules or dysfunction. 19 of 23 (82.6%) patients finished 2-3 cycles of treatment. 19 (82.6%) patients experienced treatment-related adverse events (TRAEs), with 11 (47.8%) patients experiencing grade 3-4 TRAEs. Thyroid toxicity of grade 1-2 was observed in 12 (52.2%) patients. The objective response rate (ORR) was 69.6%, and the disease control rate (DCR) was 100%.。14 (60.9%) of 23 patients underwent surgery. All patients underwent R0 resection. The pCR rate was 21.4%. The median follow-up was 22.4 months. During the follow-up period, there were no recurrences, but 3 patients died due to non-tumor-related causes. Esophagectomy following neoadjuvant immunotherapy plus chemotherapy appears to be safe and feasible in high altitude natives with resectable esophageal squamous cell carcinoma in Tibet.

DDDR-46. TARGETING TRANSGLUTAMINASE 2 (TGM2) ENHANCES SENSITIVITY OF GLIOBLASTOMA CELL LINES TO RADIOTHERAPY AND TEMOZOLOMIDE

Abstract Glioblastoma (GBM), the most aggressive and common primary brain tumor in adults, remains highly resistant to conventional therapeutics, including radiation therapy (RT), largely due to its molecular heterogeneity. Few biomarkers have been identified that successfully guide or predict treatment response. Transglutaminase 2 (TGM2), a ubiquitous multifunctional enzyme involved in numerous signal transduction pathways related to tumorigenesis, has recently been suggested to drive chemoradioresistance. Here, we investigate the effects of disrupting TGM2 by pharmacologic inhibition or CRISPR knockout (TGM2-KO) on GBM cell’s response to RT and Temozolomide (TMZ) chemotherapy. Using western blotting and clonogenic assays, we show that the allosteric TGM2 inhibitor, GK921, stabilizes p53 expression and impedes reproductive ability at IC50 and IC25 concentrations. TGM2-KO and GK921 (at IC10 and lower) sensitized GBM cell lines to RT with almost equivalent efficacy, resulting in a 2- to 3-fold suppression of clonal expansion compared to scramble controls or irradiation alone. We also demonstrate increased sensitivity of GBM cell lines to TMZ upon inhibition of TGM2 by GK921. Our findings indicate that the use of TGM2 inhibitors, such as GK921, could enhance the efficacy of RT and the potency of TMZ, positioning TGM2 as a promising therapeutic target that may improve standard treatment of GBM cells expressing TGM2.

INNV-37. REAL-WORLD OUTCOMES AMONG HIGH GRADE IDH1-MUTANT GLIOMA PATIENTS TREATED WITH AN IDH INHIBITOR

Abstract BACKGROUND Isocitrate dehydrogenase (IDH) inhibitors are transforming the treatment of patients with non-enhancing grade 2 IDH-mutant gliomas. Uncertainty remains on the utility of IDH-inhibitors in high-grade IDH-mutant glioma patients that had prior therapies and have progressive disease. METHODS From October 2020 to December 2023, we identified high-grade IDH1-mutant patients treated with off-label ivosidenib, a mutant IDH1 inhibitor. We report their clinical and imaging characteristics. RESULTS In our cohort (n=18), the patient age range was 29-68 years with male predominance (n=11). Diagnoses included astrocytoma grades 3 (n=9) or 4 (n=2), and oligodendroglioma grade 3 (n=7). The median number of progressions prior to ivosidenib initiation was 2 (range 1-7). Fifteen patients had prior surgical resection, three had biopsy. Prior treatment exposures included radiation therapy (n=15), temozolomide (n=18), lomustine (n=5), bevacizumab (n=3), etoposide (n=1), optune (n=1) and a clinical trial (n=1). Mean time from diagnosis to ivosidenib treatment was 9.6 years (95% CI, 6.7 to 16.4 years). Karnofsky performance-status score upon initiation was 80 (n=6) or 90 (n=12). Thirteen patients had >1 cm enhancing disease, five had non-enhancing disease. Ivosidenib was initiated due to enhancing disease progression (n=11), non-enhancing disease progression (n=4), a combination of both (n=2) or temozolomide intolerance (n=1). Best radiographic responses per RANO criteria were partial response (n=2), minor response (n=3), stable disease (n=7), and progressive disease (n=6). Nine patients continue ivosidenib without disease progression, with a median treatment duration of 27.5 months (95% CI, 18.0 to 33.0 months). All had FLAIR stabilization/improvement and 45% (n=4) had improved enhancing disease. Nine patients discontinued ivosidenib due to progression, with a median treatment duration of 7 months (95% CI, 3 to 9 months). CONCLUSIONS These data suggest that treatment with an IDH inhibitor can provide disease control for some high-grade IDH-mutant glioma patients who had prior therapies and progressive disease. Future studies are needed to investigate this patients population.

INNV-31. THE USE OF IVOSIDENIB IN PATIENTS WITH ENHANCING IDH1 MUTANT GLIOMAS

Abstract Ivosidenib offers a novel targeted therapy for non-enhancing IDH1 mutated gliomas following initial resection. Potential effects of IDH inhibitors on enhancing disease in clinical settings are not well established. This study characterizes a cohort of patients with IDH1 mutated gliomas with enhancing disease, who were initiated on monotherapy, off-label ivosidenib between October, 2020 to August, 2023. The cohort included 21 patients ages 29 to 73 years, 11 female and 10 male. Diagnoses represented were astrocytoma IDH1 mutant, grade 2-4 (N=9) and oligodendrogliomas IDH1 mutant, grade 2-3 (N=12). Prior treatment exposures included radiation therapy (N=11), temozolomide (N=15), bevacizumab (N=3), and treatment naïve (N=6). Time from diagnosis to ivosidenib initiation was 9.1±2.7 years. Although all patients had enhancing disease, ivosidenib was initiated due to non-enhancing disease progression (N=7), enhancing disease progression (N=13), and temozolomide intolerance (N=1). Size of enhancement by cross-section measured >1cm (N=15) and <1cm (N=6). Best radiographic responses per RANO criteria were partial response (N=3), stable disease (N=11), and progressive disease (N=7). At last contact, eleven patients were maintained on ivosidenib with no evidence of disease progression since initiation with an average treatment duration of 25.5±6.4 months and overall survival of 11.7±3.1 years. Ten patients had disease progression at median 5.2±3.1 months following ivosidenib initiation, three of whom died 16.7 (range 6.8-34.4) months after treatment initiation with an overall survival of 9.4 years (range 4.6-13.6). Adverse events from therapy included diarrhea (N=2), CK elevation (N=4), and QTc prolongation (N=2). No patients discontinued ivosidenib due to adverse events. No significant difference was detected between patients with and without disease progression due to size of enhancement (p=0.4) or prior treatment exposure (p=0.3). Future studies should include biopsies to understand the role of enhancing lesions in treatment response of IDH inhibitors.

CvTMorph: Improving Local Feature Extraction in Medical Image Registration for Respiratory Motion Modeling with Convolutional Vision Transformer.

Accurately modeling respiratory motion in medical images is crucial for various applications, including radiation therapy planning. However, existing registration methods often struggle to extract local features effectively, limiting their performance. In this paper, we aimed to propose a new framework called CvTMorph, which utilizes a Convolutional vision Transformer (CvT) and Convolutional Neural Networks (CNN) to improve local feature extraction. CvTMorph integrates CvT and CNN to construct a hybrid model that combines the strengths of both approaches. Additionally, scaling and square layers are added to enhance the registration performance. We have evaluated the performance of CvTMorph on the 4D-Lung and DIR-Lab datasets and compared it with state-of-the-art methods to demonstrate its effectiveness. The experimental results have demonstrated CvTMorph to outperform the existing methods in terms of accuracy and robustness for respiratory motion modeling in 4D images. The incorporation of the convolutional vision transformer has significantly improved the registration performance and enhanced the representation of local structures. CvTMorph offers a promising solution for accurately modeling respiratory motion in 4D medical images. The hybrid model, leveraging convolutional vision transformer and convolutional neural networks, has proven effective in extracting local features and improving registration performance. The results have highlighted the potential of CvTMorph for various applications, such as radiation therapy planning, and provided a basis for further research in this field.

Assesing health needs of women with breast cancer in a Regula Hospital Dispensary in Crete, Greece

Abstract Background Understanding the health needs of women with breast cancer is essential for tailor-made care. Socio-economic factors impact care access and outcomes. Previous research has indicated variations in healthcare experiences based on factors such as education level, employment status, and income. However, specific insights into the health needs of women with breast cancer in Crete, Greece, remain limited. Purpose The current study aimed at assessing the health needs of women with breast cancer. Methods A total of 161 women were surveyed between June 2023 and December 2023 in a regular Hospital Dispensary at a General Hospital in Heraklion, Greece. Results The majority were married (46%) and had an average of 2 children. 16% were graduates of secondary education and 42 % graduates of higher education, 33% retired and 19% full-time employees. Most participants (45%) reported a family income between 10,001 to 20,000 €, 29% under 10000 € and 26 % between 20001 to 30000 €. The majority had received additional medical treatment (75%), with surgery being the most common (30.6%). Other treatment included radiation therapy (28%), chemotherapy (23%), and hormone therapy (18%). Prevalence of comorbidities was high, with hypertension (97%), coronary heart disease (92%), cholesterol issues (43.5%), arrhythmias (82%), thyroid disease (81%), diabetes mellitus (79.5%), and bleeding disorders (43.5%) being reported. Smoking was also prevalent among participants (79.5%). Conclusions This study highlights the complex health needs of women with breast cancer in Crete region, Greece and emphasizes the prevalence of comorbidities and the importance of tailored support services and comprehensive care approaches for this population. Key messages • Considering socio-economic factors is critical in healthcare planning and intervention strategies. • Emphasizing the importance of tailored support services and comprehensive care approaches for this population.

Implant outcomes following breast conservation therapy in patients with history of augmentation mammoplasty

BackgroundIn women who are eligible, breast conservation therapy (BCT) is often the preferred local treatment for early-stage BC. Concern for implant contracture in patients undergoing BCT including radiation therapy (RT) with prior augmentation mammoplasty has been expressed in several prior studies. The exact incidence of patient dissatisfaction remains unknown. MethodsA single institution retrospective review was performed for patients with prior augmentation mammoplasty who received BCT for BC between 2010 and 2020. 77 patients met inclusion criteria. Of these, 34 were consented and completed study survey which included validated BREAST-Q modules. Data was reviewed with primarily descriptive analyses. P-values were calculated from Fisher’s exact test and Kruskal-Wallis rank sum test. Results34 patients completed study survey, with 55.9 % of patients (n=19) having silicone implants and 44.1 % (n=15) having saline. Most implants (91.1 %, n=31) were retropectoral. Median total dose of RT was 4005 cGy and median age of implants at BC diagnosis was 16 years (range 2, 40). 41 % (n=14) of patients reported dissatisfaction with breast appearance, with median BREAST-Q RASCH score for satisfaction with breasts 48 (range 20–82). No differences in breast satisfaction were seen in patients with silicone implants compared to saline (p= 0.171) although there were improved reported physical well-being chest scores in patients with saline implants (median 100 vs 89; p = 0.039). ConclusionsA large proportion of women are dissatisfied with implant appearance following BCT with RT. Future larger studies are needed to explore contributing factors for dissatisfaction including implant type, location, RT dosing and fractionation.

What Sets Uveal Melanoma Apart, and How Can We Address It? A Comprehensive Review of Pathophysiology, Diagnosis and Treatment

Uveal melanoma (UM) is a serious condition requiring immediate medical attention. It is the most common primary intraocular cancer in adults, with an incidence of around 5.2 cases per million people annually. Nearly half of UM patients develop metastatic disease, most often affecting the liver. UM refers to any malignant tumor arising from melanocytes in the uveal tract, which includes the iris, ciliary body, and choroid. Treatment options for UM depend on several factors, including tumor size, location, and the patient's overall health. These options may include radiation therapy, surgery, laser treatments, targeted therapies, and immunotherapy. UM is often described as an immune-privileged tumor, with a distinct immune profile compared to cutaneous melanoma (CM). This article aims to highlight the unique characteristics and challenges associated with this rare form of melanoma. By providing detailed information, the article seeks to enhance understanding and management of this rare form of melanoma.

Automatic delineation and prognostic assessment of head and neck tumor lesion in multi-modality positron emission tomography / computed tomography images based on deep learning: A survey

Accurately segmenting and staging tumor lesions in cancer patients presents a significant challenge for radiologists, but it is essential for devising effective treatment plans including radiation therapy, personalized medicine, and surgical options. The integration of artificial intelligence (AI), particularly deep learning (DL), has become a useful tool for radiologists, enhancing their ability to understand tumor biology and deliver personalized care to patients with H&N tumors. Segmenting H&N tumor lesions using Positron Emission Tomography/Computed Tomography (PET/CT) images has gained significant attention. However, the diverse shapes and sizes of tumors, along with indistinct boundaries between malignant and normal tissues, present significant challenges in effectively fusing PET and CT images. To overcome these challenges, various DL-based models have been developed for segmenting tumor lesions in PET/CT images. This article reviews multimodality (PET/CT) based H&N tumor lesions segmentation methods. We firstly discuss the strengths and limitations of PET/CT imaging and the importance of DL-based models in H&N tumor lesion segmentation. Second, we examine the current state-of-the-art DL models for H&N tumor segmentation, categorizing them into UNet, VNet, Vision Transformer, and miscellaneous models based on their architectures. Third, we explore the annotation and evaluation processes, addressing challenges in segmentation annotation and discussing the metrics used to assess model performance. Finally, we discuss several open challenges and provide some avenues for future research in H&N tumor lesion segmentation.

Adenomas hipofisarios no funcionantes. Incidentaloma hipofisario

Non-functioning pituitary adenomas (NFPAs) are tumors of the pituitary gland that are usually benign and show no clinical or biochemical signs of excessive hormone production. These tumors manifest clinically when they are large enough to exert pressure on surrounding structures. Among pituitary incidentaloma, NFPAs are the most common, as they are often diagnosed accidentally during imaging tests performed for other reasons. To properly evaluate these tumors and their relationship to other structures, the use of contrast-enhanced MRI is preferred. In addition, it is necessary to perform a hormonal analysis to rule out hormonal alterations and a neuro-ophthalmological examination in those cases in which the adenomas are close to the optic chiasm or cavernous sinuses, or in patients who present vision problems. In cases where the tumors are symptomless, observation is an option. However, transsphenoidal surgery is the first-line treatment for patients with symptoms or large tumors. Other options include radiation therapy and medical treatment with dopaminergic agonists and other drugs that are being explored more recently.

Recent Development of Fluoroquinolone Derivatives as Anticancer Agents.

Cancer is the second leading cause of death in the world following cardiovascular disease. Its treatment, including radiation therapy and surgical removal of the tumour, is based on pharmacotherapy, which prompts a constant search for new and more effective drugs. There are high costs associated with designing, synthesising, and marketing new substances. Drug repositioning is an attractive solution. Fluoroquinolones make up a group of synthetic antibiotics with a broad spectrum of activity in bacterial diseases. Moreover, those compounds are of particular interest to researchers as a result of reports of their antiproliferative effects on the cells of the most lethal cancers. This article presents the current progress in the development of new fluoroquinolone derivatives with potential anticancer and cytotoxic activity, as well as structure-activity relationships, along with possible directions for further development.

Trait Mindfulness and Social Support Predict Lower Perceived Stress Burden in Patients Undergoing Radiation Therapy

Purpose/ObjectivesCancer diagnosis and treatment, including radiation therapy (RT), cause significant patient stress. Mindfulness and social support have been shown to help manage the psychological effects of cancer treatment. The objective of our study was to determine the sociodemographic and clinical factors associated with stress burden in patients undergoing RT. Materials/MethodsPatients undergoing RT for cancer at a single institution were given 3 surveys to complete at the beginning of on-treatment visit. The surveys included the Perceived Stress Scale (PSS), Medical Outcomes Study Social Support Survey (MOS), and Mindfulness Attention Awareness Scale (MAAS), which were used to measure stress, social support, and trait mindfulness, respectively. Linear regression analysis was performed to determine associations between perceived stress and age, patient sex, race and ethnicity, treatment intent, disease site, trait mindfulness, and social support. Factors significant on univariable analysis were analyzed with a multivariable analysis. ResultsA total of 93 patients completed 279 surveys during treatment at a tertiary care academic institution from July to September 2019. Median scores for PSS, MOS, and MAAS were 14.6 (range: 0-31, SD: 6.9), 4.2 (range: 0-5, SD: 1.0), and 5.1 (range: 3.1-6.0, SD: 0.8), respectively. On univariable analysis, mindfulness and social support were associated with decreased stress burden, and female sex and palliative intent were associated with increased stress burden. These factors all maintained significance on multivariable analysis. ConclusionThese results suggest measures to improve mindfulness and perceived social support, such as mindfulness meditation and psychoeducational approaches, may lessen the stress burden and improve quality of life for patients undergoing RT. Future studies should analyze the longitudinal impact of individual patient characteristics, including patient sex and treatment intent, to better understand their effects on psychological maladjustment during cancer care

Epidemiological trends and socioeconomic factors in malignant peripheral nerve sheath tumors with rhabdomyoblastic differentiation: A National Cancer Database study.

e23562 Background: Malignant peripheral nerve sheath tumor with rhabdomyoblastic differentiation, also called a malignant triton tumor (MTT) is both a rare and aggressive form of cancer with both the features of peripheral nerve sheath tumors as well as rhabdomyoblasts with high recurrence rates. There is a higher risk of patients with neurofibromatosis type 1 (NF1) developing MTT. Radiation can be used to excise higher grade large MTT, however, chemotherapy still has no consensus on efficacy. Despite the rarity of MTT with rhabdomyoblastic differentiation, increased efforts to understand epidemiological trends could increase overall understanding of the malignancy. Methods: We extracted data from 50 patients diagnosed with MTT(ICD-9561-3) using the 2004-2020 National Cancer Database (NCDB) to perform a retrospective cohort analysis. We focused on various demographic factors including age, sex, race, Hispanic status, income status, educational status, insurance status, facility type and location, distance from facility, and Charleson-Deyo score using descriptive statistics. Regression analysis was used to identify incidence trends. Results: In our study of 50 patients diagnosed with MTT, a majority of the patients were male (62%), identified as White, and were of non-Spanish/non-Hispanic (90%) ethnicity. The average age at diagnosis was 49 years (SD = 20, range = 3-90) most and patients were treated in academic/research facilities (32%) or integrated network cancer programs (18%). Most patients (48%) had private insurance, with a significant number relying on government-funded programs (44%). The majority of patients (88%) underwent surgery as their primary treatment, with 30% having no residual tumor post-surgery. Additional treatments included radiation therapy (38%), chemotherapy (34%) and the most frequent primary site was the retroperitoneum (30%).The average survival time post-treatment was 35 months, with a survival rate of 43% at 2 years, 23% at 5 years, and a 15% at 10 years. Patients qualified for the top quartile of median housing income( $74,063 ≈). Conclusions: This study is the first analysis of patients with MTT, using the NCDB. It fills a gap in our understanding of this rare and aggressive disease. The majority of MTT patients were male, Caucasian, with an average age at diagnosis of 49 years, which supports previous case report descriptions. In addition, this study reveals the socio-economic factors associated with these patients who mostly earned a median income of $74,063 or more, were insured primarily by private insurance or managed programs (48%), and were treated predominantly in academic or research institutions (32%). It is necessary to continue research to further understand the influence of demographic and socio-economic factors on the diagnosis, treatments, and overall survival of patients with MTT.

Problems of late radiation injuries of the skin and possibilities of their treatment

Currently there is a problem of insufficient effectiveness of treatment of late radiation skin lesions. Possibilities of application of combined schemes of treatment of malignant neoplasms, including radiation therapy, show both good immediate and distant results, life expectancy of patients has increased. However, the issue of such remote local radiation lesions as radiation ulcers also remains relevant. Such lesions in the practice of clinical oncologists usually occur from 1-1,5 months and more after the end of the course of close-focus X-ray therapy for skin cancer. The peculiarity of radiation ulcers is that they heal extremely poorly even by secondary tension. In the pathogenesis of late radiation ulcers, along with disruption of microcirculation, the main role is played by the direct damaging effect of radiation on stem cells and, consequently, suppression of reparative processes. For this reason, such ulcerous defects are characterized by torpidity to drug and surgical treatment. The analysis of modern scientific and practical literature does not fully reveal the peculiarities of the pathogenesis of post-radiation skin lesions leading to the development of radiation ulcers. Researchers have set a goal to search for new modern methods of effective treatment of this pathology. The main purpose of the literature review was to theoretically substantiate the possibilities of including enzyme antioxidants and epidermal growth factor preparations into the complex of pathogenetic treatment of radiation skin ulcers. Superoxide dismutase (SOD) is an active enzyme-antioxidant, it neutralizes excessive free oxygen radicals, and also has a pronounced anti-inflammatory effect by means of oxidative post-radiation stress of skin tissues. Epidermal growth factor promotes cell growth and differentiation of stem cells (SC) involved in ulcer defect regeneration. Pathogenetically justified stepwise application of these drugs will improve the effectiveness of treatment of post-radiation skin ulcers. This paper presents the current information about the pathogenesis of late radiation skin ulcers, the mechanism of action of SOD, epidermal growth factor preparations, as well as the importance of the microenvironment and the homing effect in controlling the links of the pathogenesis of radiation ulcers and the possibility of their reparative regeneration.

Superoxide Dismutase Mimetic Avasopasem Manganese Enhances Radiation Therapy Effectiveness in Soft Tissue Sarcomas and Accelerates Wound Healing.

Soft tissue sarcomas (STSs) are mesenchymal malignant lesions that develop in soft tissues. Despite current treatments, including radiation therapy (RT) and surgery, STSs can be associated with poor patient outcomes and metastatic recurrences. Neoadjuvant radiation therapy (nRT), while effective, is often accompanied by severe postoperative wound healing complications due to damage to the surrounding normal tissues. Thus, there is a need to develop therapeutic approaches to reduce nRT toxicities. Avasopasem manganese (AVA) is a selective superoxide dismutase mimetic that protects against IR-induced oral mucositis and lung fibrosis. We tested the efficacy of AVA in enhancing RT in STSs and in promoting wound healing. Using colony formation assays and alkaline comet assays, we report that AVA selectively enhanced the STS (liposarcoma, fibrosarcoma, leiomyosarcoma, and MPNST) cellular response to radiation compared to normal dermal fibroblasts (NDFs). AVA is believed to selectively enhance radiation therapy by targeting differential hydrogen peroxide clearance in tumor cells compared to non-malignant cells. STS cells demonstrated increased catalase protein levels and activity compared to normal fibroblasts. Additionally, NDFs showed significantly higher levels of GPx1 activity compared to STSs. The depletion of glutathione using buthionine sulfoximine (BSO) sensitized the NDF cells to AVA, suggesting that GPx1 may, in part, facilitate the selective toxicity of AVA. Finally, AVA significantly accelerated wound closure in a murine model of wound healing post RT. Our data suggest that AVA may be a promising combination strategy for nRT therapy in STSs.

Abstract PO5-16-10: The efficacy of novel antibody-drug-conjugates on brain metastases in metastatic breast cancer patients – a multicenter real-world analysis

Abstract 15 – 30% of all patients with metastatic breast cancer (MBC) develop brain metastases (BMs). Treatment of BMs include radiation therapy and surgical resection while systemic treatment is challenging and prospective evidence for the treatment of active brain metastases is restricted to the small molecule Tucatinib. Recently, the antibody-drug-conjugates (ADCs) Sacituzumab-Govitecan (SG) and Trastuzumab-Deruxtecan (T-DXd) have shown to be highly effective in the treatment of triple-negative (SG), HER2-positive (T-DXd) and HR+/HER2- (SG and, in case of HER2-low-expression, T-DxD) MBC. However, there is only limited data, whether these macromolecules are also effective in patients with BMs. We therefore aimed to examine the efficacy of SG and T-DXd in patients with stable and active BMs in a multicenter real-world analysis. Female patients with stable or active BMs who were treated with either SG or T-DXd at the breast centers of Tuebingen University, Ulm University or Freiburg University in Germany before June 30, 2023 were included into this analysis. Data cut-off for this analysis was July 10, 2023. BMs were classified as active if they were newly diagnosed and did not require local treatment or if they were progressing and did not require local treatment. Preexisting BMs without intracranial disease progression or preexisting/newly diagnosed BMs that had been treated by surgery and/or radiotherapy directly prior to SG/T-DXd therapy were considered as stable. All patients underwent baseline magnetic resonance imaging (MRI) of the brain and received follow-up MRIs at least every three months. Growth dynamics of BMs were assessed by board certified neuroradiologists. Intracranial disease control rate (icDCR) was defined as the percentage of patients with at least intracranial stable disease at the first follow-up MRI. Intracranial progression-free survival (icPFS) was determined as the period between the first application of SG or T-DXd and intracranial disease progression or treatment cessation due to the patients’ will or the onset of intolerable toxicity. If ADC treatment was discontinued due to extracranial disease progression albeit at least stable intracranial disease patients were censored. Overall survival (OS) was defined as the period between the first application of SG or T-DXd and death. In total, 26 patients were included with a median of two prior therapy lines in the metastatic setting (range 2 – 15). 10 (38%) and 14 (54%) patients received SG and T-DXd, respectively. 2/26 (8%) patients receiving SG were consecutively subjected to T-DXd treatment. SG was applied to 12/12 patients (100%) due to triple-negative MBC and 12/16 patients (75%) treated with T-DXd were HER2-positive. The remaining 4/16 patients (25%) treated with T-DXd showed HER2 low tumor biology. 5/12 (42%) and 8/16 (50%) patients treated with SG or T-DXd had active BMs at treatment initiation. The icDCR was 33% (95% CI: 5% - 61%)/81% (95% CI: 62% - 100%) for all patients treated with SG/T-DXd and 40% (95% CI: 0% - 88%)/75% (95% CI: 43% - 100%) in case of active BMs. After a median follow-up of 7.2 months, 10/12 (83.3%) patients treated with SG and 4/16 (25%) patients subjected to T-DXd had discontinued treatment. Median icPFS was 3.1 months (95% CI: 0.4 – 5.8 months) for SG and not reached for T-DXd. 7/12 (58%) patients treated with SG and 4/16 patients (25%) treated with T-DXd died until data cut-off. Median OS was 7.2 months (95% CI: 3.0 – 11.4 months) for patients treated with SG and not reached for patients treated with T-DXd. SG and T-DXd showed promising clinical activity in both, stable and active cerebral breast cancer metastasis. Updated PFS and OS data will be reported at the meeting. Citation Format: Dominik Dannehl, Henning Schäffler, Tobias Engler, Lea Volmer, Arne Estler, Ilinca Popp, Stefanie Lorenz, Eva-Maria Grischke, Markus Hahn, Ghazaleh Tabatabai, Ingolf Juhasz-Böss, Wolfgang Janni, Sara Brucker, Florin-Andrei Taran, Andreas Hartkopf. The efficacy of novel antibody-drug-conjugates on brain metastases in metastatic breast cancer patients – a multicenter real-world analysis [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 PO5-16-10.

A Prostate Boundary Localization and Edge Denoising Algorithm

This research aimed at presenting a two-step method for prostate segmentation in TRUS images. The research used a prostate boundary localization and prostate edge denoising approach. The proposed method contribution is the use of the optimized Hodge’s method as the boundary operator and the use of the Bidirectional Exponential moving average to perform edge denoising. The results showed that the proposed method is effective in completing the prostate segmentation task. (1) The prostate region is effectively initialized and localized. (2) The recovery of noise points is accomplished and the segmentation result being consistent with the general shape of the prostate. The experimental results showed that this method can improve the overall segmentation accuracy. The process uses a combination of traditional and unsupervised methods, eliminating the need to rely on large data sets compared to current deep learning methods. The proposed method achieved excellent segmentation accuracy, with the Dice similarity coefficient (DICE) value of 0.9679, an average Intersection over Union (IoU) value of 0.9377, and an average False Positive Rate (FPR) of 0.0399. The results obtained from this study have significant implications for clinical practice. Accurate prostate segmentation is crucial for various applications, including radiation therapy planning, image-guided interventions, and computer-aided diagnosis. The proposed method has the potential to improve these applications by providing more precise and reliable prostate segmentations. However, it is important to acknowledge some limitations of this study. First, the proposed method was evaluated on a limited dataset, which may not fully represent the diversity of prostate images encountered in clinical practice. Further validation on larger datasets is necessary to assess its generalizability. Additionally, the proposed method relied on manual annotations for training, which can introduce inter-observer variability. Incorporating automated or semi-automated annotation techniques could enhance the robustness of the method

Incorporating plan complexity into the statistical process control of volumetric modulated arc therapy pre-treatment verifications.

Statistical process control (SPC) is a powerful statistical tool for process monitoring that has been highly recommended in healthcare applications, including radiation therapy quality assurance (QA). The AAPM TG-218 report described the clinical implementation of SPC for Volumetric Modulated Arc Therapy (VMAT) pre-treatment verifications, pointing out the need to adjust tolerance limits based on plan complexity. However, the quantification of plan complexity and its integration into SPC remains an unresolvedchallenge. The primary aim of this study is to investigate the incorporation of plan complexity into the SPC framework for VMAT pre-treatment verifications. The study explores and evaluates various strategies for this incorporation, discussing their merits and limitations, and provides recommendations for clinicalapplication. A retrospective analysis was conducted on 309 VMAT plans from diverse anatomical sites using the PTW OCTAVIUS 4D device for QA measurements. Gamma Passing Rates (GPR) were obtained, and lower control limits were computed using both the conventional Shewhart method and three heuristic methods (scaled weighted variance, weighted standard deviations, and skewness correction) to accommodate non-normal data distributions. The 'Identify-Eliminate-Recalculate' method was employed for robust analysis. Eight complexity metrics were analyzed and two distinct strategies for incorporating plan complexity into SPC were assessed. The first strategy focused on establishing control limits for different treatment sites, while the second was based on the determination of control limits as a function of individual plan complexity. The study extensively examines the correlation between control limits and plan complexity and assesses the impact of complexity metrics on the controlprocess. The control limits established using SPC were strongly influenced by the complexity of treatment plans. In the first strategy, a clear correlation was found between control limits and average plan complexity for each site. The second approach derived control limits based on individual plan complexity metrics, enabling tailored tolerance limits. In both strategies, tolerance limits inversely correlated with plan complexity, resulting in all highly complex plans being classified as in control. In contrast, when plans were collectively analyzed without considering complexity, all the out-of-control plans were highlycomplex. Incorporating plan complexity into SPC for VMAT verifications requires meticulous and comprehensive analysis. To ensure overall process control, we advocate for stringent control and minimization of plan complexity during treatment planning, especially when control limits are adjusted based on plancomplexity.

Comprehensive radiotherapy for pediatric Ewing Sarcoma: Outcomes of a prospective proton study

Background and purposePatients with Ewing Sarcoma (EWS) are treated with multimodality therapy which includes radiation therapy (RT) as an option for local control. We report on the efficacy after proton radiation therapy (PRT) to the primary site for localized and metastatic EWS. Materials and methodsForty-two children with EWS (33 localized, 9 metastatic) treated between 2007 and 2020 were enrolled on 2 prospective registry protocols for pediatric patients undergoing PRT. PRT was delivered by passive scatter (74 %), pencil-beam scanning (12 %) or mixed technique (14 %). Treated sites included the spine (45 %), pelvis/sacrum (26 %), skull/cranium (14 %), extraosseous (10 %), and chest wall (5 %). Median radiation dose was 54 Gy-RBE (range 39.6–55.8 Gy-RBE). Patients with metastatic disease received consolidative RT to metastatic sites (4 at the time of PRT to the primary site, 5 after completion of chemotherapy). Median follow-up time was 47 months after PRT. ResultsThe 4-year local control (LC), progression-free survival (PFS), and overall survival (OS) rates were 83 %, 71 %, and 86 %, respectively. All local failures (n = 6) were in-field failures. Tumor size ≥ 8 cm predicted for inferior 4-year LC (69 % vs 95 %, p = 0.04). 4-year PFS and OS rates were not statistically different in patients with localized versus metastatic disease (72 % vs 67 %, p = 0.70; 89 % vs 78 %, p = 0.38, respectively). ConclusionIn conclusion, LC for pediatric patients with EWS treated with PRT was comparable to that of historical patients who received photon-RT. Tumor size ≥ 8 cm predicted increased risk of local failure. Patients with metastatic disease, including non-pulmonary only metastases, received radiation therapy to all metastatic sites and had favorable survival outcomes.

Abstract 805: Employment characteristics and work ability differences by race and income before undergoing curative treatment for prostate cancer (PCW WF-1802)

Abstract Background: African American (AA) men are, on average, diagnosed with prostate cancer at younger ages and more advanced stages than white men and therefore may be at greater risk of having cancer treatment negatively impact their work ability and job opportunities. This longitudinal, observational study aims to better identify whether race, household income (< or ≥ 300% the U.S. poverty line), or work-related factors may place some men with prostate cancer at greater risk for experiencing negative employment impacts from cancer treatment and its side effects. Here we report on individual and employment-related factors by race and income prior to treatment initiation. Methods: AA and white men who were expected to undergo primary curative treatment (prostatectomy or radiation therapy) in the near future for prostate cancer were recruited through the Wake Forest NCORP Research Base (UG1CA189824, NCT03963739) between 2019 and 2023. Participants were AA or white, recently employed, expecting to be working in 6 months, and willing to disclose income status. Participants answered questions prior to treatment initiation related to employment and working conditions, work ability, and demographic characteristics. Differences in outcomes by race and income were analyzed with Fisher's exact test or t-test. Results: The baseline questionnaire was completed by 244 men; 48% AA/52% white and 64% higher/36% lower Income. Most planned treatments included radiation therapy (60%) and/or prostatectomy (41%), with no statistical differences by income or race. Higher income men were significantly more likely than lower income men to be married, have attained higher education, have a management or professional job, work full-time, be a permanent employee, salaried, eligible to retain their job under FMLA, work in an office/home, have a psychologically demanding job, and less likely to hold a physically demanding job. AA men were significantly less likely than white men to be married, have attained higher education, have a management or professional job, or work in an office/home. AA men were more continuously hopeful about the future (69%) compared to white men (52%; p=0.0079). There were no significant differences across categories in age, perceived current work ability in relation to physical (69% very good) or mental (71% very good) demands, or number of jobs held. Prior to treatment, participants reported almost optimal current work ability (mean 9.0, SD 1.2) with a range of 0 to 10 with 10 as best possible work ability. Conclusion: In this study, income category is a greater predictor than race of job characteristics that may impact employment following definitive prostate cancer treatment. Citation Format: Joanne C. Sandberg, Emily V. Dressler, Louis S. Krane, Karen M. Winkfield, Lingyi Lu, Andrew M. Mayfield, Drew C. Monitto, J. Daniel Pennington, Deimante M. Tamkus, Glenn J. Lesser. Employment characteristics and work ability differences by race and income before undergoing curative treatment for prostate cancer (PCW WF-1802) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 805.