bluuebunny/crossref_metadata_2025_split huggingface dataset:
CLRM-08 TAILORING CLINICAL TRIALS TO INCREASE PATIENT ENGAGEMENT: IMPACT ON PATIENT-REPORTED OUTCOMES IN ONCOLOGY
Authors: Khakwani Saima , Dumais Kelly 
Published: August 2023

Abstract

BACKGROUND
As regulators put more attention on patient-reported outcomes (PROs) in oncology clinical trials, it is vital to understand patient preferences and motivation for completing PROs. We investigated preferences and motivations for symptom reporting and how this may differ between participants with cancer and with other chronic non-oncology diseases.

METHODS
Participants completed an online survey focusing on preferences for using devices to report symptoms and what motivates them to complete PROs. Statistical analyses included a descriptive analysis of responses and Chi-Squared tests to examine differences between subgroups (oncology vs. participants with arthritis, diabetes, and chronic obstructive pulmonary disease).

RESULTS
Participants with cancer (N = 16) preferred using their own smartphone (31%) over going to a website (19%) or using a study-dedicated device (6%) to report symptoms, with 44% being happy with any option (44%). 88% of participants reported that receiving regular information to help manage their symptoms would motivate them the most to complete their PROs on a regular basis. Receiving a small financial compensation (81%) and knowing that their data was being reviewed by a healthcare professional (75%) were also strong motivators to complete PROs. The least preferred motivator was compensation in the form of charity donations (25%). Preference for reporting symptoms differed between subgroups (p=0.04), such that participants with cancer showed a higher preference for using their own smartphone compared to the non-oncology subgroup (N=30). The non-oncology subgroup was more likely to report notifications and alarms (p=0.04) as strategies that would encourage them to complete PROs.

CONCLUSION
This exploratory analysis suggests the importance of considering a range of symptom reporting strategies and the potential for tailoring strategies to fit patient preferences. The preference to use personal smartphones to report symptoms in participants with cancer suggests that a Bring-Your-Own-Device (BYOD) strategy may be particularly suited for oncology clinical trials.
CLRM-09 MAPPING THE DISTRIBUTION AND CLINICAL ASSOCIATIONS OF BRAIN METASTASES IN RENAL CELL CARCINOMA
Authors: Kamson David Olayinka , Feinaj Ardit , Markowski Mark , Yerrapragada Anirudh , Elias Roy , Shenderov Eugene , Bettegowda Chetan , Singla Nirmish , Ged Yasser 
Published: August 2023

Abstract
Brain metastases (BrM) commonly occur in renal cell carcinoma (RCC) and often present with hemorrhagic features. The distribution patterns of BrM in RCC and their associations with clinical outcomes remain unclear. We conducted a retrospective neuroanatomical distribution analysis combined with clinical review of our surgical RCC BrM cohort. Sixty-seven BrMs from 46patients (age 63±10years, 25males) were included. The majority of BrM (55%) were found in the left hemisphere, with frontal (45%), parietal (21%), and occipital (18%) lobes being the most commonly affected areas. Hemosiderin deposits, as detected by MRI, were present in 82% of BrM, while hemorrhage, as detected by CT, was present in 80% of BrM. Patients with solitary BrM had a higher KPS (p=0.006) and lower disease burden (p=0.004) compared to those with multiple BrM. Mean 1D and 2D(RANO) tumor dimensions were 2.0±1.1cm and 4.7±4.9cm2, respectively, and correlated with the neutrophil count at BrM diagnosis (r=0.3; p=0.01). Hemosiderin deposits were associated with larger tumors (2.6±1.0cm vs. 1.8±0.7cm, p=0.04), lower platelet counts (p=0.01), and higher hemoglobin levels (p=0.08). Shorter Brain Metastasis-Free Survival was associated with hemosiderin deposits on MRI (log-rank p=0.04) and renal vein thrombosis (RVT) in the primary specimen (log-rank p=0.002). RVT at primary diagnosis was associated with both hemosiderin deposits on MRI (p=0.05) and hemorrhage on CT (p=0.03), and CNS progression-free survival was shorter in patients with RVT (7.3±1.7 months vs. 21.0±4.7 months). When including only significant predictors, right hemispheric BrM lateralization (HR 2.6, p=0.06), hemosiderin deposits in BrM (HR 6.5, p=0.02), and IMDC risk groups (intermediate HR=2.9; poor-risk HR=25.6; p&lt;0.04) were independent prognostic factors for shorter OS on multivariable analysis. Our results demonstrate that mapping the BrM distribution o in RCC can provide clinically relevant insights. Hemosiderin deposits in BrM may have prognostic implications. Further analyses are ongoing.
CLRM-11 ALK TYROSINE KINASE INHIBITOR THERAPY AND BRAIN METASTASES IN NON-SMALL CELL LUNG CANCER: IMPACT ON TUMOR SIZE AND DISTRIBUTION
Authors: Kamson David Olayinka , Cheunkarndee Tia , Marrone Kristen , Murray Joseph , Feliciano Joy , Hann Christine , Ettinger David , Anagnostou Valsamo , Forde Patrick , Brahmer Julie , Levy Benjamin , Scott Susan , Lam Vincent 
Published: August 2023

Abstract
Non-small cell lung cancer (NSCLC) with anaplastic lymphoma kinase rearrangement (ALK+) is known to have a high propensity to form brain metastases (BrM), with over 50% of ALK+ lung cancer patients developing BrM despite effective ALK tyrosine kinase inhibitor (TKI) therapy with central nervous system (CNS) activity. Pharmacokinetic (PK) data from other CNS-active lung cancer TKIs have suggested that there may be differences in drug concentration between white and gray matter in the brain, which may play a role in BrM formation patterns and response. In this study, we aimed to compare the size and distribution of ALK+ NSCLC BrMs at diagnosis in a TKI-naïve and TKI-exposed cohort. Brain MRI data from patients with ALK+ NSCLC were retrospectively reviewed, and each tumor was marked in a standard space brain model using 3D Slicer-4.11. FreeSurfer white-gray matter atlases were used to assess BrM distribution. We found that TKI-exposed patients had significantly smaller BrM diameters than TKI-naïve patients (6.1±3.8 vs. 10.2±5.5mm, p=0.02) and were more likely to have white matter-exclusive (3.5±4.4 vs. 1.4±2.0, p=0.05) and deep white matter metastases (3.2±4.3 vs. 1.3±2.0, p=0.06). The metastatic burden was similar between the groups, while the mean number of BrM per patient was numerically higher in the TKI-exposed group (10.6±11.9 vs. 6.2±9.5; p=0.22). These findings suggest that TKI therapy may result in smaller individual lesions that are more likely to be exclusive to the white matter, where drug concentrations may be significantly lower. This suboptimal CNS distribution of TKIs in the white matter may contribute to the progression of brain metastases in ALK+ patients despite TKI therapy. Further analyses are ongoing to evaluate ALK TKIs of varying CNS penetrance and later disease time points in more granular anatomic regions.
LMAP-13 THE IMPACT OF RADIATION TREATMENT DOSE TO THE TUMOR AND NORMAL TISSUES USING POST-OPERATIVE MRI VS. MR-SIMULATION FOR RADIOTHERAPY PLANNING OF HIGH-GRADE GLIOMA
Authors: Thrower Sara , Farhat Maguy , Curl Brandon , Cifter Gizem , Shanker Mihir , Beckham Thomas , Ghia Amol , Swanson Todd , Wang Chenyang , Brock Kristy , Chung Caroline 
Published: August 2023

Abstract

BACKGROUND
Radiotherapy (RT) targets are commonly defined on post-operative (post-op) MRI registered to CT simulation images. However, changes can occur between surgery and simulation due to tumor progression and post-operative healing. In this work, we evaluate the impact of treatment planning using MR images taken at the time of CT simulation (MR-sim) versus post-op MRI.

METHODS
We evaluated 30 patients with primary HGG who received post-op MRI followed by RT planned using an MR-sim. We retrospectively delineated the gross tumor volume (GTV), clinical target volume (CTV), and normal structures on the post-op MRI and generated an experimental RT plan for these volumes. The RT plans based on post-op and MR-sim images were compared to determine the volume of tumor tissue that would have been undertreated, and the amount of normal brain tissue that would have been exposed to radiation (overtreated) had the plan been based on the post-op imaging.

RESULTS
The mean length between post-op imaging and MR-sim was 26 days (range: 12-42). A mean of 7.3cc (range 0.36cc–25.23cc) and 32.4cc (0.35–140.14cc) of the GTV and CTV, respectively, were undertreated on the post-op MRI plan compared to the MR-sim plan. The plan based on post-op target volumes resulted in a mean decrease in prescription dose coverage of the MR-sim-based GTV and CTV of 15.8% (max 72%) and 11.7% (max 57%), respectively. A mean of 14.5cc (0.04cc–53.9cc) and 47.5cc (range 2.4–179.2) of non-target brain tissue as identified on the MR-sim were included in the post-op MRI-based GTV and CTV, respectively. On average, the optic chiasm and brainstem would have received 191cGy and 117cGy more dose than intended, respectively.

CONCLUSIONS
Our findings confirm the valuable impact of RT planning using MR-sim in HGG to optimize treatment targets and reduce the exposure of normal tissue to unnecessary toxicity.
LMAP-15 INTRACRANIAL RADIOTHERAPY WITH TUCATINIB FOR BRAIN METASTASIS FROM HER2-POSITIVE BREAST CANCER: A SINGLE-INSTITUTION SERIES
Authors: Khatri Vaseem , Mills Matthew , Oliver Daniel , Yu Michael , Ahmed Kamran 
Published: August 2023

Abstract

BACKGROUND
Tucatinib, a HER-2 TKI, has demonstrated intracranial efficacy in the HER2CLIMB study. Treatment of brain metastases frequently includes stereotactic radiosurgery (SRS) or whole brain radiotherapy (WBRT); however, HER2CLIMB did not detail outcomes with RT.

METHODS
Patients who received tucatinib at our institution from 2020-2022 were identified. Patients who had brain metastases and received intracranial RT within 6 months of receiving tucatinib were included. Patients with history of prior leptomeningeal disease (LMD) were excluded. The Kaplan-Meier (KM) method was used to estimate intracranial failure (ICF), overall survival (OS), and local control (LC). Adverse events and details regarding symptomatic radionecrosis were collected.

RESULTS
Between 2020 and 2022, 50 patients were treated with tucatinib. Forty patients had diagnosed brain metastasis and received intracranial RT. Median age at tucatinib start was 51 years (range: 33-83). All patients were HER-2+, 47.5% were HR+. Fifty-four separate RT courses were delivered within 6 months of tucatinib, including 45 courses of stereotactic RT (83%) and 9 (17%) WBRT. Twenty-three patients (57.5%) underwent concurrent tucatinib and intracranial RT, defined as RT within 2 months of tucatinib initiation. Median follow up for surviving patients was 18.9 months. Fifteen patients (37%) died at the time of analysis. Median OS was 25.1 months with 24-month KM OS of 52%. Median time to ICF was 12.5 months with 24-month KM ICF of 48%. At the time of ICF, 7 patients (17.5%) developed LMD. In total, 132 discrete lesions were treated with SRS. Ten lesions (7.5%) underwent local failure, with 24-month KM LC of 82%. Three patients (9.1%) undergoing SRS developed symptomatic radionecrosis; all completely resolved with dexamethasone.

DISCUSSION
In this first series reporting outcomes with RT and tucatinib, no evidence of excess toxicity was noted. Intracranial control appears favorable compared to previous reports. Concurrent RT with tucatinib should be assessed prospectively.
LMAP-16 THE EFFECTS OF POSTOPERATIVE STEREOTACTIC RADIOSURGERY TIMING ON CLINICAL OUTCOMES IN PATIENTS WITH INTRACRANIAL METASTASES: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Nwankwo Anthony , Dang Danielle , Choe Kevin , Kanani Samir , Cohen Adam , Ziu Mateo 
Published: August 2023

Abstract
Stereotactic radiosurgery (SRS) after neurosurgical resection improves local tumor control in patients with metastatic brain cancer. However, the influence of timing on its therapeutic efficacy is unclear, and a lack of consensus and standardization limits its optimization. We performed a systematic review and meta-analysis examining publications that reported the timing of postoperative SRS for patients with intracranial metastases. Our primary outcomes included median overall survival and rates of local and regional failure, while our secondary outcomes examined the incidence of treatment-related adverse events. Correlations between median SRS timing and these variables were assessed using linear regression and publication bias was appraised via Egger’s test. Our systematic review resulted in 22 articles comprising 1338 patients who met the criteria for inclusion. The median timing of adjuvant SRS spanned 14.5 to 41 days. There was a significant positive study-level correlation of median time to SRS with regional failure (P=0.043, R2=0.32) but not with overall survival (P=0.54, R2=0.03) or local failure (P=0.16, R2= 0.14). Data regarding adverse events related to treatment was limited in the literature and there was significant heterogeneity within the reports (P&lt;0.0001). Overall, our results demonstrate institutions with a longer time between surgery and SRS had lower rates of regional failure, however, this did not affect rates of local failure or patient survival. Further research is warranted to elucidate the role of timing for postoperative SRS on oncologic outcomes as well as the factors that contribute to optimal radiosurgery workflow in this patient population.
LMAP-19 THE ROLE OF STEREOTACTIC RADIOSURGERY IN PATIENTS WITH BRAIN METASTASES FROM COLORECTAL CANCERS
Authors: Taori Suchet , Wei Zhishuo , Deng Hansen , Niranjan Ajay , Lunsford L Dade 
Published: August 2023

Abstract

BACKGROUND AND OBJECTIVES
The role of stereotactic radiosurgery (SRS) for patients with brain metastases from colorectal cancers (CRC) has not been established. The authors present a single-institution experience of CRC patients who underwent SRS with metastatic brain spread.

METHODS
We retrospectively analyzed 112 metastatic CRC patients (64 female, 57.14%) with 450 brain metastases that were treated with Gamma Knife SRS between 2000-2022. The median age at SRS was 63 years (range: 28-86) and the median Karnofsky Performance Score (KPS) was 80 (range: 60-100). The primary sites were colon (86 patients, 76.79%) and rectal (26 patients, 21%). Three patients underwent hypo-fractionated SRS (3 sessions) with a median margin dose of 27 Gy (range: 27- 30). All other patients underwent single-session SRS with a median margin dose of 18 Gy (range: 11-20).

RESULTS
The median patient survival after SRS was 7 months (range: 1-174). Ninety-eight (87.5%) patients expired at last follow up and 15 patients (15.31%) died related to progressive intracranial disease. KPS &lt; 80 at SRS presentation (p=0.03, HR: 0.63, 95% CI: 0.41-0.96) was associated with inferior overall survival using multivariate analysis. Seventeen patients (15.18%) had documented local tumor progression after SRS, at a median time of 7 months (range: 3-34) between SRS and progression. Twenty-six patients (23.21%) developed new brain metastases at a median of 5 months (range: 2-26) between SRS and new tumor detection. KPS ≥ 80 (p=0.05, HR: 0.96, 95% CI: 0.93-0.99), and &lt; 3 brain metastases at SRS presentation (p&lt;0.01, HR: 3.62, 95% CI: 1.53-8.56) were associated with better distant tumor control on multivariate analysis. The incidence of adverse radiation effects was 5.36%.

CONCLUSIONS
SRS effectively controls brain metastases from CRC with a low risk of treatment-related toxicity, allowing patients to focus on primary disease management. During follow-up, the development of progressive or additional metastases can be safely treated by repeat SRS.
NEIM-08 MODELING COMPETITION BETWEEN SUBPOPULATIONS WITH VARIABLE DNA CONTENT IN RESOURCE LIMITED MICROENVIRONMENTS
Authors: Katira Parag , Rentzeperis Frederika , Beck Richard , Pinto Ana Forero , Nowicka Zuzanna , Tagal Vural , Teer Jamie , Scanu Elisa , Pasetto Stefano , Veith Thomas , Fiandaca Giada , Fritz Yi , Devine Karen , Barnholtz-Sloan Jill , Farinhas Joaquim , Gomes Ana , Andor Noemi 
Published: August 2023

Abstract
Resource limitations shape the outcome of competitions between heterogeneous pre-malignant cells. One example of such heterogeneity is in the ploidy (DNA content) of pre-malignant cells. High-ploidy cells need more resources, to synthesize increasing amounts of DNA, RNA and proteins. To model how subpopulations with variable DNA-content compete in the resource limited environment of the human brain we developed a stochastic state-space model of the brain (S3MB). The model discretizes the brain into voxels, whereby the state of each voxel is defined by 8+ variables that are updated over time, including stiffness, glucose and proliferating cells of various DNA content. Well established Fokker-Planck partial differential equations govern the spatial distribution of resources and cells. We applied S3MB on sequencing and imaging data obtained from a primary GBM patient. We sequenced four surgical specimens collected during the 1st and 2nd surgeries of the GBM and used HATCHET to quantify its clonal composition and how it changes between the surgeries. HATCHET identified two aneuploid subpopulations of ploidy 1.98 and 2.29 respectively. The low-ploidy clone was dominant at the time of the first surgery and became even more dominant upon recurrence. MRI images were available before and after each surgery and registered to MNI space. T1 post and T2 flair scans acquired after the 1st surgery informed tumor cell densities per voxel. Magnetic Resonance Elastography scans and PET/CT scans informed stiffness and Glucose access per voxel. We performed a parameter search to recapitulate the GBM’s tumor cell density and ploidy composition before the 2nd surgery. Results suggest that the high-ploidy subpopulation had a higher Glucose-dependent proliferation rate, but a lower Glucose-dependent death rate, resulting in spatial differences in the distribution of the two subpopulations. Our results contribute to a better understanding of how genomics and microenvironments interact to shape cell fate decisions.
SDPS-13 CELL LINE STUDY OF NUCLEOSOME-BASED BIOMARKERS IN THE DIAGNOSIS AND DETECTION OF RELAPSES IN GLIOBLASTOMA
Authors: Decarpentrie Jonathan , Van den Ackerveken Priscilla , Govaerts Adrien , Lobbens Alison , Beine Edeline , Donis Nathalie , Herzog Marielle , Douxfils Jonathan 
Published: August 2023

Abstract
Currently, glioblastoma (GBM) diagnosis and monitoring rely on neuroimaging and histopathological confirmation. However, overall survival has not improved in last decades due to therapeutic failure and to a lack of biomarkers for relapses’ detection. Liquid biopsies (i.e. blood or cerebrospinal fluid) using nucleosomes-containing-histone post-translational modifications (PTMs) have the potential to become valuable biomarkers for diagnosis and monitoring GBM. Four glioblastoma cell lines (SF-126, U-87MG, U-118MG, and U-138MG) compared to a healthy microglia cell line (HMC3) and other solid cancer cell lines including pancreas (MIA PaCa-2), liver (HepG2), and cervix/uterus (HeLa) have been analyzed to identify their epigenetic profile. Nucleosomes were extracted and analyzed with the Nu.Q® Discover immunoassays platform (Belgian Volition) addressing 13 histone-PTMs. Quantitative results of PTMs expression were normalized on quantification of total nucleosomes (H3.1-nucleosomes). The immunoassay identified three candidate biomarkers compared to control cell lines (n=4): citrullinated-histone H3 (H3R8Cit) (control=4.68% ; GBM=13.88% ; p&lt;0.05), phosphorylation of H3S10 (H3S10Ph) (control=2.31% ; GBM=5.57% ; p&lt; 0.05), and a trend in H3K4Me2 elevation (control=0.43% ; GBM=1.07% ; p=0.066) in GBM cell lines(n=4). These results were confirmed by western blot. In addition, principal component analysis revealed a segregation between GBM and control cells, mainly driven by these three PTMs. Moreover, to demonstrate the capacity of the Nu.Q® assays to quantitatively monitor PTMs, GBM cell line SF-126 (n=3) was treated with an EZH2 inhibitor (responsible of H3K27 methylation) (iEZH2). After 24 hours and 48 hours of exposure, the level of expression of H3K27Me3 – expressed as ratio of total nucleosomes was decreased by 32% (control=14.67%±0.58% ; iEZH2=10.00%±1.73% ; p&lt;0.05) and 41% (control=15.33%±1.53% ; iEZH2=9.00%±0.00% ; p&lt;0.05), respectively. Those results were also confirmed by western blot analysis. In conclusion, we identified three specific in vitro epigenetic-based marks of GBM and demonstrated that the Nu.Q® technology is a valuable tool to monitor the degree of PTMs expression.
SDPS-14 CLINICAL FEATURES AND OUTCOME IN CHILDREN WITH CHOROID PLEXUS CARCINOMA-A SINGLE CENTER EXPERIENCE
Authors: Li Miao , Du Shuxu , Sun Yanling , Wu Wanshui , Sun Liming 
Published: August 2023

Abstract

OBJECTIVE
To investigate the clinical features, treatment and outcome in pediatric choroid plexus carcinoma (CPC) patients.

METHODS
Twelve children with CPC confirmed by pathology who were admitted to Beijing Shijitan Hospital from January 2017 to October 2022, were included. The last follow-up was December 31, 2022. Kaplan-Meier method was adopted for survival analysis.

RESULTS
Among the 12 patients, 4 were males and 8 females. The median age at diagnosis was 29.7 (range, 5.8-119.6) months, with 8 cases less than 3 years old at the time of diagnosis. Nine cases were supratentorial, and 3 infratentorial. The tumor was located in ventricular system in 6 cases, external involvement of brain parenchyma in 6 cases. Two cases experienced metastases (M+) and 10 M0 at the time of diagnosis. All patients received tumor resection, with 8 cases GTR and 4 NTR. Five cases received chemotherapy only and 7 patients radio-chemotherapy after surgery. At last follow-up, 8 cases experienced tumor recurrence or progression, and 4 died. The mean OS were (56.7±8.8) months, The 1, 3, 5-year OS were (83.3%±10.8)%、(66.7%±13.6)%, and (66.7%±13.6)%, respectively. The mean PFS time were (24.3±7.2) months, The 1, 3-year PFS were (41.7%±14.2)% and (33.3%±13.6)%, respectively. Univariate analysis showed the OS were poorer in children with infratentorial tumors than supratentorial tumors (χ2 =8.562, P = 0.003). And the OS was also lower in patients who received chemotherapy only than those who received both radiotherapy and chemotherapy (χ2 =8.488, P =0.004). The difference in PFS between groups were not significant (P&gt;0.05).

CONCLUSION
CPC is very rare and with poor prognosis in children. Children with infratentorial tumors and who received chemotherapy only tend to have poorer OS. Due to the small sample size, further clinical trials need to be developed to verify.