Radiotherapy Data Research Articles

Danish and Swedish National Data Collections for Cancer – Solutions for Radiotherapy

Collecting large amounts of radiotherapy (RT) data from clinical systems is known to be a challenging task. Still, data collections outside the original RT systems are needed to follow-up on the quality of cancer care and to improve RT. This paper aims to describe how RT data is collected nationally in Denmark and Sweden for this purpose and gives an overview of the stored information in both countries' national data sources.Although both countries have clinical national quality registries with broad coverage and completeness for many cancer diagnoses, some were initiated already in the seventies, and less than one in ten includes quantitative information on RT to a level of detail useful for more than basic descriptive statistics. Detailed RT data can, however, be found in Denmark's DICOM Collaboration (DcmCollab) database, initiated in 2009 and in Sweden's quality registry for RT launched in 2023 (SKvaRT). Denmark has collected raw DICOM data for all patients enrolled in clinical trials, with files being directly and automatically transferred to DcmCollab from the original data sources at each RT centre. Sweden collects aggregated RT data into SKvaRT for all patients undergoing RT in Sweden, with DICOM files being transferred and selected alpha-numeric variables forwarded via a local intermediate storage database (MIQA) at each hospital. In designing their respective solutions, both countries have faced similar challenges regarding which RT variables to collect and how to technically link clinical systems to their data repositories. General lessons about how flexibility currently is balanced with storage requirements and data standards are presented here together with future plans to harvest real-world RT data.

Nonmetallic Carbon Fiber-Reinforced Polyetheretherketone Implants Vs Titanium Implants: Analysis of Clinical Outcomes and Influence on Postoperative Radiotherapy Planning in Metastatic Spine Tumor Surgery.

Titanium has been the conventional implant material of choice for fixation in both primary and metastatic spine tumor surgeries (MSTS). However, these implants result in artifact generation during postoperative computed tomography or magnetic resonance imaging, resulting in poor planning of radiotherapy (RT) and suboptimal tumor surveillance. Carbon fiber-reinforced polyetheretherketone (CFR-PEEK) implants have gained momentum for instrumentation in MSTS due to their radiolucent properties. In this study, the perioperative outcomes, postoperative imaging artifacts, and dosimetric data of CFR-PEEK implants to titanium implants were compared to assess for potential benefits in postoperative RT planning in patients undergoing MSTS. This is a retrospective study involving 62 patients who underwent operations for MSTS. The cohort of CFR-PEEK fixations (n = 20) was compared with a series of patients operated using titanium implants (n = 42). Patient-related data, including demographics, tumor pathology and extent of morbidity, intraoperative data, functional outcome, and RT-related data, were recorded for both groups. Primary outcome measures for RT data were amount of artifact generated on postoperative imaging and the time taken to contour them. All patients were followed up postoperatively for a minimum of 2 years or until death, whichever was earlier. Both groups had similar clinical outcomes for pain and overall survival predictability preoperatively (P = 0.786). The mean number of levels instrumented by titanium screws was 5.69 ± 2.64, while for CFR-PEEK screws it was 4.26 ± 1.05. Mean volume of artifact generated during postoperative computed tomography was 73.4 ± 50.43 mm3 in the titanium group and 20.0 ± 20.7 mm3 in the CFR-PEEK group (P < 0.001). The mean time taken to contour the artifacts was 17.3 ± 5.84 minutes in titanium group and 9.60 ± 7.17 minutes in CFR-PEEK group (P = 0.049). Our study confirms that CFR-PEEK screws significantly reduce artifact generation and the time taken to contour them during postoperative RT planning while delivering equivalent clinical and functional outcomes as compared with standard titanium implants.

DIPG-63. RE-IRRADIATION FOR PROGRESSIVE DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG): THE SPANISH EXPERIENCE

Abstract BACKGROUND Despite advances in its biological understanding, current treatments for diffuse intrinsic pontine glioma (DIPG) have shown minimal impact on overall survival in this fatal disease. Radiotherapy (RT) is the only therapeutic intervention that has demonstrated efficacy in improving symptoms and prolonging progression-free survival. In addition, re-irradiation (rRT) is emerging as an alternative treatment for advanced disease, albeit palliative. This study presents the Spanish experience with re-irradiation in DIPG. METHODS We retrospectively reviewed demographic, clinical and RT data of patients with DIPG treated with rRT in Spain. RESULTS Between April 2015 and December 2023, 44 Pediatric patients with progressive DIPG underwent rRT in 16 Spanish institutions. Median time from diagnosis to progression was 10 months (range, 4.2-24.3). Median dose of rRT was 20 Gy (range, 18-40) in a median of 2 Gy fractions (range, 1.3-4). Twenty-one patients (47.7%) underwent additional treatments in addition to RT. Clinical and radiological improvements were observed in 77.3% and 60% of cases, respectively. Treatment was well tolerated with only 3 patients experiencing severe toxicity (one requiring a VP-shunt, and two finalizing rRT due to bronchoaspirations). Median overall survival was 15.1 months (range, 8.2-61.2), with a median time from rRT to death of 4.2 months (range, 0.6-10.3). Compared to patients who experienced earlier relapses, those who relapsed after 10 months exhibited superior overall survival (21.8 vs. 12.9 months; p &amp;lt; 0.001%), and a longer interval from rRT to death (6.2 vs. 3.8 months; p = 0.058). There was no survival benefit in patients receiving additional treatments. CONCLUSIONS rRT effectively improves symptoms and prolongs survival in many progressive DIPG patients. However, the ideal candidates for rRT remain undefined. The retrospective nature of the study makes it difficult to assess the true impact of additional treatments. We encourage prospective research into the combination of rRT with other therapies.

Safety and immunological effects of ablative radiotherapy followed by pembrolizumab in patients with advanced adrenocortical carcinoma.

TPS4630 Background: Adrenocortical carcinoma (ACC) is a rare and aggressive cancer with poor prognosis. While pembrolizumab is a NCCN recommended treatment, our prior study showed no benefit in patients with liver metastases (NCT02673333).1 Preclinical evidence suggests combining liver-directed radiation therapy (RT) with pembrolizumab might enhance anti-tumor immunity.2 Our current study will assess the safety and describe preliminary efficacy data for ablative RT to symptomatic liver metastases followed by treatment with pembrolizumab in patients with advanced ACC. Methods: This is a single-center pilot study. Main inclusion criteria include: adult patients with metastatic ACC with symptomatic liver metastases, presence of extrahepatic metastases, ECOG 0-1. Ablative RT in 5 or 10 once daily fractions will be delivered over 1 to 2 weeks; pembrolizumab treatment (200mg Q3W) will begin one week after RT completion. The primary objective is to evaluate the safety of treatment with ablative RT followed by pembrolizumab. The study will include a 6 patient safety lead-in, with 10 to 12 patients enrolled in total. The secondary endpoint, efficacy, is defined as the objective response (partial and complete response) according to RECIST v1.1, in the hepatic and extrahepatic disease. Correlative objectives include evaluation of the innate and adaptive immune response during treatment through analysis of pre- and on-treatment blood and tumor tissue samples, circulating tumor (ct) DNA analyses, and PD-L1 and next-generation sequencing testing in pre-treatment tumor tissue samples to evaluate for biomarkers of response and resistance. This trial began enrollment in 9/27/2023, with 3 patients enrolled to date.

Abstract PO4-17-05: Patterns of care: radiotherapy after breast conserving surgery and the use of endocrine therapy for screen-detected ductal carcinoma in situ (DCIS) in the UK

Abstract Background The use of adjuvant radiotherapy (RT) and endocrine therapy (ET) in the management of pure ductal carcinoma in situ (DCIS) remains controversial. We investigate how the use of adjuvant RT after breast conserving surgery (BCS) and use of adjuvant ET (in BCS and mastectomy patients) has changed over time. Methods A prospective cohort SQL database of 11,284 patients (the Sloane Project) diagnosed 2003-2012 with screen-detected DCIS in the UK was interrogated for use of adjuvant RT and ET over time and association with factors reported to be predictive of recurrence (patient age, DCIS nuclear grade, size, comedo necrosis, resection margins), as well as institution of surgery, travel time to radiotherapy facility, Index of Multiple Deprivation and outcome (provided by the National Disease Registration Service, NDRS). RT data by site were confirmed with more recent data from the National Audit of Breast Cancer in Older Patients (NABCOP), which looked at patterns of care and outcomes for women aged 70 years and over, compared with those aged 50-64 in England and Wales. Results Among the 7,949 women (70.6%) treated by BCS, post-operative adjuvant RT was given to 4,939 (62.1%); RT use after BCS increased over time (R2 =0.92; p&amp;lt; 0.01). RT use was associated with year of diagnosis (p &amp;lt; 0.01), younger age at diagnosis (p &amp;lt; 0.01), larger DCIS size (p &amp;lt; 0.01), presence of comedo necrosis (p &amp;lt; 0.01), higher nuclear grade (p &amp;lt; 0.01) and presence of microinvasion (p &amp;lt; 0.01). Adjusted analyses showed the most significant factor for RT after BCS was the surgery institution. Travel time to RT facility, Index of Multiple Deprivation and final radial margin were not associated with RT use. When compared with the more recent data from the NABCOP, a marked variation in radiotherapy use across hospitals remains. Ipsilateral recurrence rate varied significantly by hospital, with some of the difference associated with RT utilisation. ET was prescribed in 1313 women (12%), more often following BCS than mastectomy (p &amp;lt; 0.001), with significant variation by institution and a decline in the use of ET over time. Conclusion Marked geographic variation in the use of RT and ET after surgery for DCIS persists in the UK and is likely due to physician choice rather than other factors such as travel times to RT facilities. This is contributing to geographic variation in ipsilateral recurrence rates, suggesting the need for adoption of more authoritative guidelines to support clinical decision-making. Consistent national practice could provide auditable performance standards for adjuvant therapy of screen detected DCIS and contribute to more uniform patient care. Citation Format: Karen Clements, David Dodwell, Elinor Sawyer, Ramsey Cutress, Nisha Sharma, Abeer Shaaban, Alastair Thompson. Patterns of care: radiotherapy after breast conserving surgery and the use of endocrine therapy for screen-detected ductal carcinoma in situ (DCIS) in the UK [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 PO4-17-05.

Improving Quality Assurance in a Radiation Oncology Using ARIA Visual Care Path.

Errors and incidents may occur at any point within radiotherapy (RT). The aim of the present retrospective analysis is to evaluate the impact of a customized ARIA Visual Care Path (VCP) on quality assurance (QA) for the RT process. The ARIA VCP was implemented in June 2019. The following tasks were customized and independently verified (by independent checks from radiation oncologists, medical physics, and radiation therapists): simulation, treatment planning, treatment start verification, and treatment completion. A retrospective analysis of 105 random and unselected patients was performed, and 945 tasks were reviewed. Patients' reports were categorized based on treatment years period: 2019-2020 (A); 2021 (B); and 2022-2023 (C). The QA metrics included data for timeliness of task completion and data for minor and major incidents. The major incidents were defined as incorrect prescriptions of RT dose, the use of different immobilization systems during RT compared to the simulation, the absence of surface-guided RT data for patients' positioning, incorrect dosimetric QA for treatment plans, and failure to complete RT as originally planned. A sample size of approximately 100 was able to obtain an upper limit of 95% confidence interval below 5-10% in the case of zero or one major incident. From June 2019 to December 2023, 5300 patients were treated in our RT department, an average of 1300 patients per year. For the purpose of this analysis, one hundred and five patients were chosen for the study and were subsequently evaluated. All RT staff achieved a 100% compliance rate in the ARIA VCP timely completion. A total of 36 patients were treated in Period A, 34 in Period B, and 35 in Period C. No major incidents were identified, demonstrating a major incident rate of 0.0% (95% CI 0.0-3.5%). A total of 26 out of 945 analyzed tasks (3.8%) were reported as minor incidents: absence of positioning photo in 32 cases, lack of patients' photo, and absence of plan documents in 4 cases. When comparing periods, incidents were statistically less frequent in Period C. Although the present analysis has some limitations, its outcomes demonstrated that software for the RT workflow, which is fully integrated with both the record-and-verify and treatment planning systems, can effectively manage the patient's care path. Implementing the ARIA VCP improved the efficiency of the RT care path workflow, reducing the risk of major and minor incidents.

379 Meningioma Molecular Groups Predict Response to Adjuvant Radiotherapy Following Surgery

INTRODUCTION: Aside from surgery, radiotherapy (RT) remains the only treatment for meningiomas. However, patient selection for adjuvant RT remains controversial. METHODS: We utilized publicly available molecular datasets of meningiomas and generated de novo DNA-methylation and RNA-sequencing data. Meningiomas were classified into different molecular and methylation groups based on the methodologies of their original publications (Nassiri et al. [2021], Bayley et al. [2022], Choudhury et al. [2022], Sahm et al.[2017]) and progression-free survival (PFS) following surgery with and without adjuvant RT were analyzed. RESULTS: A total of 2029 meningiomas from 11 different institutions with adjuvant RT data were included. Adjuvant RT was associated with improved PFS in WHO grade 1 meningiomas following subtotal resection (STR), WHO grade 2 meningiomas following gross total resection (GTR) or STR, and immunogenic (COCA1) and NF2-wildtype (COCA2) meningiomas following STR. Multivariable analysis using Cox proportional hazards regression models showed that having a meningioma belonging to a hypermetabolic (COCA3) (HR 2.49, 95% CI 1.71-3.62), or proliferative (COCA4) (HR 3.77, 95% CI 2.78-5.10) group were associated with worse PFS when controlling for age, gender, extent of resection, and receipt of adjuvant RT. Meningiomas belonging to DKFZ MC-intermediate, MC-malignant, MenGC, and UCSF hypermitotic groups were also associated with worse outcomes. These relationships held true even in subgroup analysis with only WHO grade 2 meningiomas and following propensity score matching for the same clinical covariates above. Nearly all molecular and methylation classifications predicted 5-year PFS following surgery and adjuvant RT (area under the curve [AUC] 0.61-0.72) better than WHO grade (AUC 0.51). CONCLUSIONS: Molecular classification improves outcome prediction for meningiomas following surgery and adjuvant radiotherapy, supporting the rationale for molecularly informed treatment decisions and clinical trial stratification.

Prospective results for 5-year survival and toxicity of moderately hypofractionated radiotherapy with simultaneous integrated boost (SIB) in (very) high-risk prostate cancer

PurposeHigh-risk (HR) prostate cancer patients usually receive high-dose radiotherapy (RT) using a two-phase sequential technique, but data on a simultaneous integrated boost (SIB) technique are lacking. We prospectively evaluated the long-term results of urinary (GU) and digestive (GI) toxicity and survival data for high-dose RT using a SIB technique in HR and very high-risk (VHR) prostate cancer. MethodsPatients were treated using an SIB technique in 34 fractions, at a dose of 54.4 Gy to the pelvis and seminal vesicles and 74.8 Gy to the prostate, combined with 36 months of androgen-depriving therapy in a prospective multicenter study. Acute and late GU and GI toxicity data were collected. Overall survival (OS), biochemical-relapse-free survival (bRFS), loco-regional-relapse-free survival (LRRFS), metastasis-free-survival (MFS) and disease-free-survival (DFS) were assessed. ResultsWe recruited 114 patients. After a median follow-up of 62 months, very few patients experienced acute (M0-M3) (G3-4 GU = 3.7 %; G3-4 GI = 0.9 %) or late (M6-M60) severe toxicity (G3-4 GU = 5.6 %; G3-4 GI = 2.8 %). The occurrence of acute G2 + GU or GI toxicity was significantly related to the consequential late G2 + toxicity (p < 0.01 for both GU and GI). Medians of OS, bRFS, LRRFS, MFS and DFS were not reached. At 60 months, OS, bRFS, LRRFS, MFS and DFS were 88.2 % [82.1; 94.7], 86.0 % [79.4 %;93.2 %], 95.8 % [91.8 %;99.9 %], 87.2 % [80.9 %;94.0 %] and 84.1 % [77.2 %;91.6 %] respectively. ConclusionSIB RT at a dose of 54.4 Gy to the pelvis and 74.8 Gy to the prostate is feasible, leading to satisfying tumor control and reasonable toxicity in HR and VHR prostate cancer.

NIMG-73. RADIOGRAPHIC CHANGES AFTER RADIATION THERAPY IN SUBTOTALLY RESECTED ATYPICAL MENINGIOMAS

Abstract BACKGROUND Adjuvant radiotherapy (RT) has been shown to improve outcomes after subtotal resection (STR) of atypical meningioma, but little is known about how tumors evolve on magnetic resonance imaging (MRI) and whether this correlates with RT response. METHODS We retrospectively identified histologically confirmed cases of WHO Grade II atypical meningioma at a large academic institution from 2004-2020 who underwent subtotal resection and received radiation. Clinicodemographic, surgical, RT, and histopathologic data were collected, as well as clinical outcomes, with a median follow-up time of 69 months (IQR 61). Patients were stratified by external beam RT (EBRT) and stereotactic radiosurgery (SRS). Radiographic data included tumor location, cerebral edema, susceptibility changes, leptomeningeal enhancement, calcification, necrosis, and time to recurrence. Progression was defined by radiology report. RESULTS Of 31 patients with STR for newly diagnosed atypical meningioma, 65% (20 of 31) received RT and 11 of 20 (55%) received EBRT while nine received SRS. Of the convexity/parasagittal meningiomas (N=10), 40% demonstrated venous sinus invasion. 65% (N=13) of cases were treated upfront; the other seven progressed at a median 9.4 months before undergoing RT. Post-RT, 74% decreased in size (N=5) or stabilized (N=9); imaging was not available for one case. Recurrence after RT was observed in five cases. 11 cases developed restricted diffusion at median onset of 24.9 months; 7 developed adjacent leptomeningeal enhancement at median onset of 14.7 months, of which 86% (6 of 7) received SRS. Other patterns included adjacent nodular (N=3) and linear (N=2) enhancement, and adjacent confluent T2 signal (N=4); these could potentially represent radiation-related changes. Only one case developed calcification after 70 months. CONCLUSIONS Atypical meningiomas exhibit variable patterns of evolution after RT which may predict treatment outcomes. Multivariate analysis is planned to correlate radiographic changes with pathology characteristics, RT modality, and time to recurrence.

PATH-52. MENINGIOMA MOLECULAR GROUPS PREDICT RESPONSE TO SURGERY AND RADIOTHERAPY

Abstract INTRODUCTION Aside from surgery, radiotherapy (RT) remains the only accepted treatment for meningiomas. However, patient selection for adjuvant RT remains controversial. We aimed to evaluate whether novel molecular and methylation groups could more accurately predict outcomes following surgery and adjuvant RT compared to WHO grade using a large clinical-molecular dataset. Method: We utilized publicly available, clinically annotated molecular datasets of meningiomas and generated de novo DNA-methylation and RNA-sequencing data. Meningiomas were classified into different molecular and methylation groups based on the methodologies of their original publications (Nassiri et al. [2021], Bayley et al.[2022], Choudhury et al.[2022], Sahm et al.[2017]) and progression-free survival (PFS) following surgery with and without adjuvant RT were analyzed. RESULTS A total of 2029 meningiomas from 11 different institutions with adjuvant RT data were included. Adjuvant RT was associated with improved PFS in WHO grade 1 meningiomas following subtotal resection(STR) and WHO grade 2 meningiomas following gross total resection(GTR) or STR. Multivariable analysis using Cox proportional hazards regression models showed that having a meningioma belonging to a hypermetabolic (MG3)(HR 3.63, 95%CI 1.47-8.99), or proliferative (MG4)(HR 7.24, 95%CI 2.84-18.49) molecular group were associated with worse PFS following surgery and adjuvant RT when controlling for age, gender, WHO grade, and extent of resection. Meningiomas belonging to DKFZ MC-intermediate, MC-malignant and UCSF hypermitotic methylation groups were also associated with worse outcomes. These relationships held true even in subgroup analysis with only WHO grade 2 meningiomas and following propensity score matching for the same clinical covariates above. Nearly all molecular and methylation classifications predicted 5-year PFS including following surgery and adjuvant RT (area under the curve [AUC] 0.61-0.72) better than WHO grade (AUC 0.51). CONCLUSIONS Molecular classification improves clinical outcome prediction for meningiomas following surgery and adjuvant radiotherapy, supporting the rationale for molecularly informed treatment decisions and potential clinical trial stratification.

A national repository of complete radiotherapy plans: design, Results, and experiences

Background Previously, many radiotherapy (RT) trials were based on a few selected dose measures. Many research questions, however, rely on access to the complete dose information. To support such access, a national RT plan database was created. The system focuses on data security, ease of use, and re-use of data. This article reports on the development and structure, and the functionality and experience of this national database. Methods and materials A system based on the DICOM-RT standard, DcmCollab, was implemented with direct connections to all Danish RT centres. Data is segregated into any number of collaboration projects. User access to the system is provided through a web interface. The database has a finely defined access permission model to support legal requirements. Results Currently, data for more than 14,000 patients have been submitted to the system, and more than 50 research projects are registered. The system is used for data collection, trial quality assurance, and audit data set generation. Users reported that the process of submitting data, waiting for it to be processed, and then manually attaching it to a project was resource intensive. This was accommodated with the introduction of triggering features, eliminating much of the need for users to manage data manually. Many other features, including structure name mapping, RT plan viewer, and the Audit Tool were developed based on user input. Conclusion The DcmCollab system has provided an efficient means to collect and access complete datasets for multi-centre RT research. This stands in contrast with previous methods of collecting RT data in multi-centre settings, where only singular data points were manually reported. To accommodate the evolving legal environment, DcmCollab has been defined as a ‘data processor’, meaning that it is a tool for other research projects to use rather than a research project in and of itself.

Impact of Salvage Versus Palliative Dose Bridging Radiation Therapy on Local Control and Overall Survival in Patients with DLBCL Receiving CD19 CAR T Cell Therapy.

In patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), radiation therapy (RT) can be used to "bridge" patients during the period of chimeric antigen receptor T cell (CAR T) manufacturing. Although RT has been shown to improve local control (LC) in patients who receive RT versus do not, it is unknown whether there is an optimal dose. This was a retrospective study of patients with DLBCL who received bridging RT and CAR T cell therapy between 8/2021 and 12/2022 at a single institution (IRB #202103122). Patient, disease, and treatment characteristics were abstracted. PET/CT and laboratory data were collected at various time points. RT data including dose, planning target volume (PTV), and body volume receiving 2Gy and 4 Gy were tested for associations with LC, overall survival (OS), cytokine release syndrome (CRS) and immune effect cell-associated neurotoxicity syndrome (ICANS). Statistical tests were performed using Python libraries. Twenty-two patients with DLBCL were included for analysis. The median patient age was 68 (range 35-82) and the median prior lines of failed therapies was two. All patients had successful apheresis and subsequent CAR T manufacturing. No patients died before CAR T infusion. All patients had a pre-radiation PET/CT scan that showed Deauville 5 disease. Patients with limited stage disease received salvage dose RT (EQD2∼40Gy, n = 8) while patients with advanced disease received palliative dose RT (n = 14). The median PTV volume was 1332 cm3. With a median follow-up of 156 days (IQR 63 - 252 days) from CAR T infusion, 10 patients had died and six progressed at an RT target. A higher salvage RT dose was not associated with LC at the day 30 PET or day 90 PET time points. In a Cox regression model, no independent variable, including RT dose, was significantly associated with LC or OS, but post-RT residual target SUV trended toward an association with OS (HR 6.2, 95% CI 0.9 - 471.0, p = 0.06). Post-RT LDH was associated with CRS grade (ρ = -0.39, p = 0.05). Other non-significant associative trends were noted between CRS grade and post-RT absolute lymphocyte count (ALC) (ρ = - 0.33, p = 0.09) and residual target SUV max (ρ = - 0.37, p = 0.08) and between ICANS grade and pre- to post-RT LDH change (ρ = -0.38, p = 0.06) and post-RT lymphocyte count (ρ = 0.36, p = 0.07). In an exploratory analysis of body volume receiving integral doses of 4Gy or 2Gy and pre- and post-RT ALC change, it appeared that higher integral dose did lead to larger decreases in ALC (ρ = -0.32, p = 0.15 and ρ = -0.3, p = 0.18, respectively). In this small series of patients with r/r DLBCL treated with bridging RT prior to CAR T therapy, RT dose was not associated with LC. However, higher post-RT target residual SUV was associated with worse OS. The impact of post-RT LDH on CRS and ICANS grades should be explored further.

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.

Lung Cancer Treatment Trends During the Coronavirus Disease 2019 (COVID-19) Pandemic: A Claims and Order Data Analysis (2019–2021)

IntroductionLung cancer is treated using systemic therapy, radiation therapy (RT), and surgery. This study evaluates how utilization of these modalities and cancer stage at initial treatment shifted from 2019 to 2021. MethodsClaims for lung cancer treatment were extracted from the database of a national health care organization offering Medicare Advantage health plans and paired with enrollment data to determine utilization rates. Seasonally adjusted rates were trended, with monotonicity evaluated using Mann-Kendall tests. Using contemporaneous prior authorization order data, the association between year and the patient’s cancer stage at the time of the initial RT or surgery order was evaluated through univariable and multivariable analyses. ResultsThe study considered 140.9 million beneficiary-months of data. There were negative and significantly monotonic trends in utilization of RT (p = 0.033) and systematic therapy (p = 0.003) for initial treatment between January 2020 and December 2021. Analysis of RT and surgery order data revealed that the patients were significantly (p < 0.001) more likely to have advanced (stage III or IV) cancer at the time of their surgery order in 2020 and 2021 than in 2019. After adjusting for urbanicity, age, and local income, a significant relationship between year of the initial order and presence of advanced cancer at the time of ordering was found for surgery orders placed in 2020 (p < 0.001) and 2021 (p < 0.01), but not for RT orders. ConclusionsThere was a per-capita reduction in lung cancer treatment in 2020 and 2021, and patients receiving initial orders for surgery after the onset of the pandemic had more advanced cancer.

Retinopathy, Optic Neuropathy, and Cataract in Childhood Cancer Survivors Treated With Radiation Therapy: A PENTEC Comprehensive Review

Few reports describe the risks of late ocular toxicities after radiation therapy (RT) for childhood cancers despite their effect on quality of life. The Pediatric Normal Tissue Effects in the Clinic (PENTEC) ocular task force aims to quantify the radiation dose dependence of select late ocular adverse effects. Here, we report results concerning retinopathy, optic neuropathy, and cataract in childhood cancer survivors who received cranial RT. A systematic literature search was performed using the PubMed, MEDLINE, and Cochrane Library databases for peer-reviewed studies published from 1980 to 2021 related to childhood cancer, RT, and ocular endpoints including dry eye, keratitis/corneal injury, conjunctival injury, cataract, retinopathy, and optic neuropathy. This initial search yielded abstracts for 2947 references, 269 of which were selected as potentially having useful outcomes and RT data. Data permitting, treatment and outcome data were used to generate normal tissue complication probability models. We identified sufficient RT data to generate normal tissue complication probability models for 3 endpoints: retinopathy, optic neuropathy, and cataract formation. Based on limited data, the model for development of retinopathy suggests 5% and 50% risk of toxicity at 42 and 62 Gy, respectively. The model for development of optic neuropathy suggests 5% and 50% risk of toxicity at 57 and 64 Gy, respectively. More extensive data were available to evaluate the risk of cataract, separated into self-reported versus ophthalmologist-diagnosed cataract. The models suggest 5% and 50% risk of self-reported cataract at 12 and >40 Gy, respectively, and 50% risk of ophthalmologist-diagnosed cataract at 9 Gy (>5% long-term risk at 0 Gy in patients treated with chemotherapy only). Radiation dose effects in the eye are inadequately studied in the pediatric population. Based on limited published data, this PENTEC comprehensive review establishes relationships between RT dose and subsequent risks of retinopathy, optic neuropathy, and cataract formation.

Radiotherapy Is Associated With Improved Overall Survival in Adult Pineoblastoma: A SEER Database Analysis.

Pineoblastomas (PBLs) are rare high-grade tumors treated variably with surgery and/or radiation. The role of surgical extent of resection and radiotherapy (RT) in adult PBL remains unclear. We queried the Surveillance, Epidemiology, and End Results (SEER) database to assess these variables' effects on overall survival (OS) in adult PBL. The SEER (1975-2016) database was queried for adult patients with diagnosis of PBL (ICD-0-3: 9362/3). Variables extracted included age, sex, race, geographical region, extent of tumor resection, RT, chemotherapy (CT), and OS data. Comparisons were performed with the χ2 test for categorical variables, Cox proportional hazards models to assess the association of clinical variables on OS, and Kaplan-Meier curves were generated. A total of 201 patients with PBL were identified with mean age 40.0 years (interquartile range 27.0-51.0) and most patients being male (53%) and Caucasian (77%). 101 (50%) patients received RT, and gross total resection was achieved in 83 (41%). Age stratification by decade revealed statistically significant poorer OS in patients aged ≥70 years. In bivariate analysis, RT with or without surgery was associated with improved 5-year OS compared with no RT (77.3% vs. 63.2%, P= 0.020). In multivariate analysis, age was a poor prognostic factor for OS (P < 0.001) and RT did appear to improve survival (P= 0.020). Extent of surgical resection was not significantly associated with improved survival. In adult patients with PBL, RT may offer an OS benefit irrespective of surgery or extent of surgical resection. Patients ≥70 years of age are associated with poorer OS.

An End-to-End Natural Language Processing System for Automatically Extracting Radiation Therapy Events From Clinical Texts

Real-world evidence for radiation therapy (RT) is limited because it is often documented only in the clinical narrative. We developed a natural language processing system for automated extraction of detailed RT events from text to support clinical phenotyping. A multi-institutional data set of 96 clinician notes, 129 North American Association of Central Cancer Registries cancer abstracts, and 270 RT prescriptions from HemOnc.org was used and divided into train, development, and test sets. Documents were annotated for RT events and associated properties: dose, fraction frequency, fraction number, date, treatment site, and boost. Named entity recognition models for properties were developed by fine-tuning BioClinicalBERT and RoBERTa transformer models. A multiclass RoBERTa-based relation extraction model was developed to link each dose mention with each property in the same event. Models were combined with symbolic rules to create a hybrid end-to-end pipeline for comprehensive RT event extraction. Named entity recognition models were evaluated on the held-out test set with F1 results of 0.96, 0.88, 0.94, 0.88, 0.67, and 0.94 for dose, fraction frequency, fraction number, date, treatment site, and boost, respectively. The relation model achieved an average F1 of 0.86 when the input was gold-labeled entities. The end-to-end system F1 result was 0.81. The end-to-end system performed best on North American Association of Central Cancer Registries abstracts (average F1 0.90), which are mostly copy-paste content from clinician notes. We developed methods and a hybrid end-to-end system for RT event extraction, which is the first natural language processing system for this task. This system provides proof-of-concept for real-world RT data collection for research and is promising for the potential of natural language processing methods to support clinical care.

Primary Hepatic Lymphoma: Role of Low-Dose Radiotherapy at a Single Institution with Genetic Characterization and Paired Literature Review

Purpose/Objective: Primary hepatic lymphomas (PHL) are an extremely rare form of non-Hodgkin Lymphoma (NHL) for which there are no established treatment guidelines, with available literature largely comprised of small case reports. Therefore, we evaluate our institutional experience treating PHL within the context of existing literature to better understand treatment modalities, role of radiotherapy (RT), and outcomes. Traditionally, radiotherapy for indolent lymphomas has involved treatment of up to 2400cGy in 12 fractions, however the use of low-dose radiotherapy of 400cGy in 1-2 fractions has been increasingly utilized. However to our knowledge, use of low-dose RT for liver lymphomas has not previously been reported in the literature. Materials/Methods: We conducted a single institutional retrospective analysis of all PHL patients (pts) diagnosed from 2000-2021 with a biopsy-proven liver lesion without other lymphomatous solid organ involvement, except for concurrently diagnosed splenic lymphomas. Subgroup analysis was performed for diffuse large B-cell lymphoma (DLBCL) and indolent lymphomas, which included marginal zone (MZL), follicular (FL), and low-grade B-cell lymphoma (BCL), NOS. Univariable (UVA) and multivariable analysis (MVA) for overall survival (OS) was performed using the Cox proportional hazards model. A literature review was also conducted using key words "liver", "lymphoma", and "treatment" to identify all available reported cases of PHL. An institutional targeted sequencing database was queried to identify patients with PHL of DLBCL histology. Results: We identified 30 PHL pts within the institutional cohort and 192 pts from comprehensive literature review. Sixteen patients were male (53%), and 25 (83%) were ECOG 0. Twenty five (83%) were Lugano Stage I, 3 (10%) were Stage III, and 2 (7%) were Stage IV. Six (20%) patients had bulky disease and 3 (10%) had nodal involvement. Systemic therapy was the most common treatment modality with 20 patients (67%), and 4 patients (13%) each received surgery, radiation and observation in our institutional cohort. In the paired literature review, 96 patients (50%) received systemic therapy, 69 (36%) underwent surgery, 10 (5%) received radiation and 11 (6%) underwent observation. Seventeen (57%) of patients were alive and 5 (17%) lost to follow-up within our institutional cohort, compared with 97 patients (51%) alive and 3 (2%) lost to follow-up. Median survival in our cohort was 6 years, compared with 2 years among the literature review cohort. Subgroup analysis of DLBCL included 15 pts (Table 1). On MVA for OS, only ECOG score (p=0.02) and Lugano stage (p=0.04) remained significant. Subgroup analysis of the indolent lymphoma group included 9 pts (Figure 1). On MVA for OS, only age remained significant. Six DLBCL patients with available targeted sequencing data were identified, with 4 mutations mutated more than once: TP53 (50%), MEF2B (33%), P2RY8 (33%), and IRF8 (33%). Pathway mapping of genetic mutations was notable for alterations in cell cycle pathway genes TP53 and ATM (17%). No other pathways had greater than one genetic alteration. Conclusion: PHLs are a rare subtype of NHL without clear treatment consensus. Primary hepatic DLBCL is predominantly treated with chemotherapy in both our institutional experience and as reported in the literature, with reasonable disease control. Importantly, indolent PHL patients in the institutional cohort have been treated with various modalities including low-dose radiotherapy, which appears to achieve comparable disease control. However radiotherapy was not utilized as a modality for indolent PHL within the literature review. Therefore, this is the first report of the use of low-dose radiotherapy for treatment of indolent liver lymphomas. Our RT data is limited by short follow-up duration of RT pts compared to pts who received chemotherapy, surgery or observation. However, our results are encouraging for the consideration of low-dose radiotherapy as a management option for appropriate patients with indolent PHL. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Retinopathy, Optic Neuropathy and Cataract in Childhood Cancer Survivors Treated with Radiotherapy: A Report from the Pediatric Normal Tissue Effects in the Clinic (PENTEC) Initiative

<h3>Purpose/Objective(s)</h3> Few reports describe the risks of late ocular toxicities following radiation therapy (RT) for childhood cancers despite their impact on quality of life. The Pediatric Normal Tissue Effects in the Clinic (PENTEC) ocular task force aims to quantify the radiation dose dependence of select late ocular adverse effects. Here, we report preliminary results concerning retinopathy, optic neuropathy, and cataract in childhood cancer survivors who received cranial RT. <h3>Materials/Methods</h3> A systematic literature search was performed using PubMed, Medline, and Cochrane Library databases for peer-reviewed studies published from 1980-2014 related to childhood cancer, radiotherapy, and ocular endpoints including dry eye, eye pain, keratitis/corneal injury, conjunctival injury, cataract, retinopathy, eye muscle damage, eyelid fibrosis/atrophy, and optic neuropathy. This initial search yielded abstracts for 2941 studies, 260 of which were selected as potentially having useful outcomes and RT data. Treatment and outcome data were extracted and used to generate normal tissue complication probability (NTCP) models. <h3>Results</h3> We identified sufficient data to generate NTCP models for three endpoints: retinopathy, optic neuropathy, and cataract. Based on limited data, the model for development of retinopathy suggests 5% and 50% risk of toxicity at 42 Gy and 62 Gy, respectively. The model for development of optic neuropathy suggests 5% and 50% risk of toxicity at 57 Gy and 64 Gy, respectively. More extensive data were available to evaluate the risk of cataract, which we separated into self-reported versus ophthalmologist-diagnosed cataract. The models suggest 5% and 50% risk of self-reported cataract at 12 Gy and >40Gy, respectively, and of ophthalmologist-diagnosed cataract at 0 Gy and 9 Gy, respectively. <h3>Conclusion</h3> Radiation dose effects in the eye are poorly studied in the pediatric population. Based on limited published data, this PENTEC comprehensive review establishes relationships between radiotherapy dose and subsequent risks of retinopathy, optic neuropathy, and cataract. A lack of consistent radiotherapy data and outcome reporting in the literature prevented investigation of other ocular endpoints.

Real-World Utilization of Radiation Therapy (RT) in Multiple Myeloma (MM): An Analysis of the Connect® MM Registry

<h3>Purpose/Objective(s)</h3> RT is an important therapeutic modality utilized at various stages along the treatment continuum in MM. However, there has been no national study of RT utilization and data on the factors that influence use are lacking due to its palliative nature and the fact that RT can be used multiple times over the course of MM treatment. The Connect® MM Registry is a largely community-based registry that provides a unique opportunity to evaluate real-world use and factors that influence RT use in MM treatment. <h3>Materials/Methods</h3> The Connect MM Registry is a large, US, multicenter, prospective observational cohort study of patients (pts) aged ≥ 18 y with newly diagnosed MM from 250 community, academic, and government sites. This analysis investigated Registry pts who received RT. RT utilization was captured quarterly over the entire course of pt treatment, in the first 6 months from study enrollment and in the last 6 months prior to death. Data from 9/28/2009 — 2/4/2021 were used in this analysis. <h3>Results</h3> The Connect MM Registry included 3011 pts of whom 903 (30%) received RT at any time. Twenty-one percent (636/3011) received RT within the first 6 months of study enrollment and 16% (241/1526) within the last 6 months before death (among all death pts). Overall, pts were predominantly white (83%), male (57%), with a median age of 67 y (range 24 – 94) and received a triplet anti-MM regimen (55%). At baseline, most common indications for RT were pain (65%), impending fracture (13%), or neurologic compression (12%). On multivariable analysis, overall RT use was significantly less common in pts with Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 – 1 vs 2+ (odds ratio [OR], 0.58; <i>P</i> = 0.0014) and more common in ISS stage I + II vs III pts (OR, 1.61; <i>P</i> = 0.0009). We observed no statistically significant difference regarding pt age, sex, race/ethnicity, insurance status, geographic region, intent to transplant, or use of novel anti-MM agents in first line of treatment. In the first 6 months after study enrollment, there was more than double the odds of RT use in pts with ISS I+II vs III (OR, 2.07; <i>P</i> < 0.001) and in pts with ECOG PS 0–1 vs 2+ (OR, 0.46; <i>P</i> < 0.001). No other sociodemographic or clinical factors studied were significant. In the 6 months before death, the only factor associated with increased RT use was increasing lines of MM therapy (OR, 1.19; <i>P</i> < 0.001). <h3>Conclusion</h3> These results from the CONNECT MM Registry, representative of real-world practice, show that even in the era of novel anti-MM agents, RT is used frequently for pt care. RT use is dictated by clinical factors, including PS and disease stage, rather than sociodemographic factors. Earlier in MM diagnosis, RT may be used as an adjunct to palliate symptoms (poor PS) or to delay systemic therapy (early stage). Toward the end of life, RT is more frequently used for palliation, with limited systemic options after multiple lines of therapy.