Site Of Disease Research Articles

Prevalence of somatic PIK3CA mutations in hormone receptor-positive metastatic breast cancer: The Indian experience.

e13047 Background: The phosphatidylinositol 3-kinase (PI3K) inhibitors have been found to improve survival outcomes in hormone receptor-positive metastatic breast cancer (MBC) and are FDA-approved in this setting after progression on hormonal therapy. However, real-world data from India on the prevalence of PIK3CA mutations is scarce. Methods: This is a retrospective study including patients with hormone receptor-positive breast cancer registered at our center between January 2017- and December 2023 who developed metastatic disease on follow-up after getting appropriate treatment (adjuvant /neoadjuvant) as per institutional protocol. The PIK3CA mutation testing was done on the biopsy specimen. FDA-approved therascreen PIL3CA RGQ PCR kit from Qiagen was used and the assay is a real-time qualitative PCR test for the detection of 11 mutations phosphatidylinositol 3-kinase catalytic subunit alpha (PIK3CA) gene (Exon 7: C420R; Exon 9: E542K, E545A, E545D [1635G>T only], E545G, E545K, Q546E, Q546R; and Exon 20: H1047L, H1047R, H1047Y) using genomic DNA (gDNA) extracted from formalin-fixed, paraffin-embedded (FFPE) breast tumor tissue. The clinical demographics of patients with PIK3CA mutations were extracted from the hospital database and represented descriptively. Results: A total of 80 consecutive patients with hormone-positive breast cancer at relapse were screened and 26 were found to have PIK3CA mutations (32.5%) of which 24 were female (92.3%). The median age of patients with mutated PIK3CA cases was 50 years (range: 31 to 72 years). The clinical stage of disease at presentation was: stage II in 11.5%, IIIA in 23.1%, and IIIB in 65.4% of cases. The median time of relapse was 21 months from diagnosis (range: 10 to 42 months). The disease sites at relapse were multiple in 23 patients (88.46%) [including central nervous system (CNS) relapse in 3 patients) and CNS (brain) only in 3 patients (11.54%). The mutations detected included H1047R (3140A>G at exon 20) in 8 cases, E545K (1633 G>A at exon 9) in 5 cases, Q546R (1637 A>G at exon 9) in 4 cases, E542K (1624 G>A at exon7) in 3 cases and synchronous mutations (E542K/E545K at Exon 7) in 3 cases and (H1047R/H1047L at exon 20 ) in 3 cases. Only eight patients received alpelisib with fulvestrant due to financial constraints. Conclusions: This is the first Indian study that describes the prevalence of PIK3CA mutations in hormone-positive breast cancer at relapse. Around one-third of patients harbor this mutation and 23.1% of cases have CNS involvement at relapse. The most common PIK3CA mutation detected was H1047R (exon 20) followed by E545K (exon 9).

Development of a novel methodology to assess response to lymphoma treatment in real-world data.

e19081 Background: Innovation in the use of real-world data (RWD) for regulatory purposes is an important provision of 21st Century Cures Act. Numerous initiatives to enhance RWD methodologies in oncology drug development are ongoing, including evaluation of treatment response assessment to support effectiveness research. Blinded independent central review (BICR) standardizes response assessment in clinical trials, and corresponding RWD methodologies are needed. This study assess feasibility of BICR using RWD, and evaluates a novel, standardized treatment response methodology among patients with diffuse large B-cell lymphoma (DLBCL). Methods: A retrospective multisite chart review identified adult patients with DLBCL treated with first-line chemoimmunotherapy in US (01JAN2015-31DEC2022). Clinical data, including physician-reported response, were abstracted from medical charts and positron emission tomography-computed tomography (PET-CT) reports at treatment initiation and first response assessment. Lugano 2014 criteria, such as standardized uptake value (SUV) and Deauville score, were extracted and converted to an algorithm (rwLugano). Absence of normal tissue SUV in PET-CT reports was addressed using published values for background, mediastinum, and liver to facilitate a real-world Deauville (rwDeauville) score for rwLugano classification. PET-CTs underwent deidentified digital image transfer for BICR using Lugano 2014 criteria by two lymphoma radiologists. Descriptive analyses assessed BICR feasibility and completeness of rwLugano data elements. Results: Six oncology practices, comprising 77 physicians, abstracted medical records and PET-CT reports for 185 patients. PET-CT scans were available for BICR for 174/185 (94%) patients (41% female, mean age 66 years). BICR discordance for Deauville score at baseline and initial response occurred in 7% (12/174) and 29% (50/174), respectively. For response assessment per Lugano, BICR discordance occurred in 9% (16/174), and were further adjudicated by a third party. Lugano discordance was often related to interpretation of marrow activity and/or new disease sites, highlighting variability in lymphoma treatment response assessment. Medical record review found Deauville score charted for 97 (56%) patients at baseline and 145 (83%) at first response. Tumor SUV was complete (174/174, 100%) at baseline and for all patients (63/63, 100%) not charted as CR at first response. Thus, 29 patients (17%) required calculation of rwDeauville at first response, providing data to calculate rwLugano for all patients in the final cohort (174/174, 100%). Conclusions: This study suggests BICR, though resource intensive, can be performed, and the component measures necessary to assess response per Lugano criteria can be obtained using RWD. Accordingly, rwLugano warrants further analysis for concordance with BICR- and physician-reported response.

Large language foundation models encode clinical radiation oncology domain knowledge: Performance on the American College of Radiology Standardized Examination.

e13585 Background: The integration of Large Language Models (LLMs) into healthcare and medical education will represent a significant paradigm shift, offering transformative potential in how medical knowledge is accessed and assimilated. These models, however, have not yet been systematically trained, tested, or validated on complex medical information such as sub-specialty medical examinations. This study explores the performance of seven major LLMs in clinical radiation oncology using residency in-training exams. Methods: In this study, the 2021 American College of Radiology (ACR) Radiation Oncology In-Training Exam (TXIT) was used to evaluate the performance of various LLMs, including OpenAI's GPT-3.5-turbo, GPT-4, GPT-4-turbo, three Meta's Llama-2 models (7 billion, 13 billion, and 70 billion parameter), and Google's PaLM-2-text-bison. The ACR provided the publicly available national scoring for this exam. The exam comprised 298 questions across 13 domains, including clinical radiation oncology (195 questions, 65.4%). The exam was processed through each LLM via an application programming interface. LLM-generated answers were analyzed by clinical disease sites and compared to Radiation Oncology trainee performance and stratified by Post-Graduate Year (PGY) 2-5. Results: LLMs showed varied performance in the overall clinical radiation oncology domain, with OpenAI's GPT-4-turbo having the best performance with 68.0% correct answers, GPT-4 61.0%, GPT-3.5-turbo 48.0%, PaLM-2-text-bison 40.0%, and then the three Llama-2 models (70b 37.0%, 13b 38%, 7b 26%). GPT-4-turbo performed superiorly to lower-level (PGY2 51.6%, PGY3 61.6%) and comparably to upper-level radiation oncology trainees (PGY4 64.1%, PGY5 68.3%). Notably, GPT-4-turbo demonstrated 7.0% improvement over its predecessor GPT-4. LLMs scored the lowest in the gastrointestinal, genitourinary, and gynecology domains and highest in the bone and soft tissue, central nervous system and eye, and head, neck, and skin domains. Conclusions: GPT-4-turbo demonstrates clinical accuracy comparable to upper-level and superior to lower-level trainees in nearly all clinical domains. Conversely, Llama2 foundation models demonstrate overall worse performance than Level 1 (PGY2) trainees. Score discrepancies across disease site domains may be due to data availability, complexity of medical conditions, quality and quantity of training datasets, and interdisciplinary data inputs. Future research will need to evaluate the performance of models that are fine-tune trained in clinical oncology. This study also underscores the need for rigorous validation of LLM-generated information against established medical literature and expert consensus, necessitating expert oversight in their application in medical education and practice.

Characterization of molecular response and progression in patients with metastatic HR+/HER2- breast cancer receiving endocrine therapy and CDK4/6 inhibitors using a high-sensitivity tumor-informed assay.

3052 Background: Tumor-informed circulating tumor DNA (ctDNA) assays, designed to track patient (pt) specific variants identified by tumor sequencing, offer enhanced sensitivity compared to traditional assays focused on driver genes. This approach enables precise ctDNA quantification, facilitating early detection of molecular progression and innovative strategies in metastatic breast cancer (mBC). Methods: HR+/HER2- mBC pts receiving standard endocrine therapy + CDK4/6 inhibitors (CDKi) were enrolled in a prospective observational cohort (2018–2023). Plasma samples were collected at baseline (BL), within 30 days (d) and ~q3 months with restaging scans. Archival tumor WES was used to design personalized panels for ctDNA monitoring. The primary endpoint was time to treatment failure (TTF). Results: Of 51 pts analyzed (median age 60 years [range 38-88], 1/2L [75/20%], visceral disease 63%, palbo-/ribo-/abemaciclib 76/22/2%), tumor-informed panels were successfully designed for 43 (1 failed WES, 7 failed QC), detecting BL ctDNA in 39 (91%). The median BL estimated variant allele fraction (eVAF) was 0.5% (0.006–17.9) and was associated with liver metastases but no other covariates (e.g. bone-only disease, history of 1ry endocrine resistance [ER]). Higher BL eVAF predicted shorter TTF (HR 1.14 CI 95% 1.05–1.23, p<0.01). Most pts had eVAF decreases below BL in the first 30 d (78%) and before the first scan (89%; median 90 d, 23–158). Early increases above BL did not significantly predict TTF, with 3/8 cases showing prolonged responses. ctDNA clearance was observed in 11/39 (28%) pts at a median of 172 d (14–410) and predicted longer TTF (HR 0.06, CI 95% 0.01–0.45, p<0.01; median TTF not reached vs 14.5 mo for pts with and without clearance), with treatment failure (TF) rates of 0% vs 40%, and 8% vs 80%, at the 1- and 2-year landmarks, respectively. Clearance was not associated with any clinical covariate (i.e. disease sites, therapy line, CDKi, history of 1ry ER). For any sample irrespective of the trajectory, higher eVAF ratios to BL predicted shorter lead times to TF, though with poor correlation (r2 0.08, p=0.01). eVAF ratios to BL >1, >0.5 and <0.5 at any timepoint had median lead times to TF of 76 d (Q1–Q3 25–135), 133 d (41–360), and 326 d (174–471). A complete analysis of ctDNA dynamics and operating parameters will be presented along with RECIST 1.1 evaluation and WES-based genomic subgroups. Conclusions: ctDNA levels and changes on therapy are prognostic and high sensitivity tumor-informed assays expand the proportion of pts who can be monitored. ctDNA clearance identified pts with better outcome and might inform pt follow up and interventional strategies. Reappraisal of existing early response cutoffs, with limited precision for individual decision making, may be necessary with more sensitive assays.

Stereotactic radiosurgery (SRS) for non-small cell lung cancer (NSCLC) in the oncogene-addicted era: A real-world UK tertiary center experience.

e14011 Background: 30-50% of NSCLC patients develop brain metastases (BM). Re-evaluation of the role of SRS is required with evolving understanding of molecular subtypes of NSCLC and increasing intracranial efficacy of systemic agents. Methods: We conducted a retrospective analysis of NSCLC patients receiving SRS at our centre from 05/16-11/23. Primary objective was median overall survival (mOS months). Analysis was performed on Prism 10.1.1. Multivariate analysis was conducted using Cox Proportional Hazards Regression, with age, gender, KPS, BM size, total BM volume and oncogene status as predictor variables. Extraction from medical records was undertaken by authors, with local R&D committee approval. Results: 237 patients were evaluable. 59% (N=139) were oncogene-addicted (oNSCLC) and 41% (N=98) non-oncogene-addicted (non-oNSCLC). Median duration of follow up was 43.3m. m OS was 11.9m overall. For oNSCLC mOS was 13.1m vs 8.8m for non-oNSCLC (HR 1.49, P=0.02). mOS was 20.7m for EGFR sensitizing NSCLC (N=48) vs 10.5m without (HR 1.40 P=0.12). mOS for ALK+ (N=22) was 29.3m vs 11.6m for non-ALK+ (HR 1.90, P=0.05). mOS for KRAS+ (N=32) was 11.6m vs 12.0m without (HR 0.91, P=0.68). Significantly inferior mOS was seen for single (N=186 [78%]) vs multiple (N=51[22%]) SRS courses (8.4m vs 38.8m, [HR 0.34 P=<0.0001]). SRS at diagnosis of BM (N=118) had a mOS of 12.3m vs at nadir (N=9, not reached [HR0.44, P=0.18]), progression on 1st line TKI (N=31, 22.1m [HR 1.1, P=0.79]) and at any other time (N=157, 7.8m [HR 1.33, P=0.11 ]). There was no significant difference in survival for patients diagnosed with brain metastases at the diagnosis of metastatic disease compared to those who developed brain metastases during their disease course (12.3m vs 10.6m [HR 1.18, P=0.33]). Survival of those with 1 site of metastatic disease (18.3m) was numerically improved compared to those with 2 (10.7m, HR 1.26, P=0.25) sites, and statistically significant compared to those with 3 (10.1m, HR 1.69, P<0.02) and ≥4 (4.4m, HR 4.41, P<0.0001) sites. Conclusions: Median OS in oNSCLC was superior to non-oNSCLC, driven by numerically superior survival in EGFR+ and ALK+ cohorts. Significantly improved OS was observed in patients with multiple vs single SRS treatments, however this may be confounded by biases. Patients treated with SRS at nadir had numerically superior OS to those treated at other timepoints, however this must be interpreted with caution due to small sample size. Further prospective research is needed to interrogate these findings and guide local therapies in NSCLC with BM. [Table: see text]

MRI compared to 123I-MIBG scan for detection of central nervous system relapse in neuroblastoma.

10040 Background: Neuroblastoma (NB) relapsing in the central nervous system (CNS), though uncommon, is historically incurable. However, a multimodality approach has improved long term survival (1). Timely detection of CNS relapse may reduce or prevent morbidity and mortality. In most centers, surveillance for NB includes whole-body MIBG scans but does not require dedicated anatomical brain imaging. At Memorial Sloan Kettering Cancer Center (MSK), head MRI at regular intervals is standard. The objective of this retrospective study was to determine the optimal imaging modality for detecting CNS relapse in NB. Methods: After MSK IRB approval, records of patients with CNS NB seen at MSK from 2004-2023 were evaluated. In most cases, relapse was diagnosed at other institutions before referral to MSK. Analyzed data included symptoms and findings on brain CT/MRI and MIBG scans. Results: Of 206 patients with MIBG-avid CNS NB, 7 were excluded because they had CNS disease at diagnosis. For the remaining 199 patients, median time to CNS relapse from diagnosis was 18 months. 132 (66%) patients had CNS relapse at a median of 9.8 months after achieving complete remission. In 67 patients with prior systemic progression, median time to CNS relapse was 10.9 months from the last relapse. Relapse was isolated to CNS in 130/199 (65%) patients. 118 (59%) patients had neurological symptoms at time of CNS disease; 81(41%) were asymptomatic, relapse being detected on surveillance scans. Multiple (>1) parenchymal lesions were noted in 74 (37%), diffuse leptomeningeal disease without parenchymal involvement in 15 (7%) and solitary lesions in 110 (55%) patients. Median diameter of the largest lesion was 2.7 (range <0.5-6.8) cm. Anatomical imaging was performed with MRI (65%), CT (14%) or both (34%). Of those undergoing both scans, CNS relapse was missed on CT in 4/67 (6%) patients. 137 patients had MIBG scans before resection of CNS relapse. All sites of CNS disease noted on MRI/CT were positive by MIBG in 46 (33%) patients. However, MIBG scan was either totally or partly negative in 69 (50%) and 22 (16%) patients, respectively. Even for lesions ≥2cm in diameter, MIBG was completely negative in 27/57 (47%). MIBG positivity did not correlate with age, size >2cm, MYCN amplification or ALK mutation status (p>0.05 for each). Lesions <1cm and infratentorially located were more likely to be negative on MIBG scan (p<0.05). Lesions in symptomatic patients, dural lesions and hemorrhagic lesions were more likely to be positive on MIBG scan (p< 0.05). Conclusions: CNS relapse is isolated to the brain in most patients. MIBG scan has poor sensitivity for the detection of CNS NB, regardless of size or location. Although CT or MRI are both effective in detecting CNS relapse, the former can miss some lesions. We recommend brain MRI for surveillance of high-risk NB for ≥2 years after initial diagnosis or last systemic relapse. 1. J. Neurooncology 97:409, 2010.

Safety, tolerability and efficacy of 212Pb-DOTAMTATE as a targeted alpha therapy for subjects with unresectable or metastatic somatostatin receptor-expressing gastroenteropancreatic neuroendocrine tumors (SSTR+ GEP-NETs): A phase 2 study.

4020 Background: 212Pb-DOTAMTATE is a Targeted Alpha Therapy (TAT) in clinical development for subjects with SSTR+ neuroendocrine tumors. A phase I dose-escalation study has already been completed (Delpassand et al. J Nucl Med 2022). TAT holds the promise to improve outcomes versus Peptide Receptor Radionuclide Therapy (PRRT) with beta-emitters like 177Lu-DOTATATE, currently considered the standard of care for subjects with GEP-NETs. Methods: ALPHAMEDIX 02 is a Phase II, open-label, multicenter study evaluating the safety, tolerability and efficacy of 212Pb-DOTAMTATE in PRRT-naïve (Cohort 1, N = 36) and PRRT-refractory (Cohort 2, Target N = 30) subjects with histologically confirmed unresectable or metastatic GEP-NETs, positive somatostatin analogue imaging and at least 1 site of measurable disease per RECIST 1.1. 212Pb-DOTAMTATE was administered at 67.6 μCi/kg per cycle, with a maximum activity administered per cycle of 5.5 mCi every 8 weeks, for up to 4 cycles. Primary endpoints include overall response rate (ORR) per RECIST1.1, and incidence and severity of adverse events (AEs). Secondary endpoints include progression free survival, overall survival , and health-related quality of life. Initial results of the already completed cohort 1 are presented. Results: In cohort 1, 17 out of 36 subjects with metastatic SSTR+ GEP-NETs achieved a confirmed response (ORR 47.2% (32.0-63.0%)). In the Phase I trial, five out of eight PRRT- naïve subjects with SSTR+ GEP-NETs treated with the same regimen of 212Pb-DOTAMTATE achieved a response (ORR 62.5% (30.6-86.3%)): the combined ORR from both studies is 50% (22 out of 44, 95%-CI:36% - 64%). Median Duration of Response (DOR) has not been reached in both studies. Four out of five subjects (80%) with confirmed response in Phase I had a DOR of ≥ 12 months. In the ongoing Phase II study the response follow-up for 10 subjects with confirmed response is currently shorter than 6 months: so far 7 out of 17 subjects (41%) with confirmed response had a DOR of ≥ 6 months, and one of these subjects had a DOR of ≥ 12 months. Lymphocytopenia is a lead cause of the 59% grade 3 and 4 AEs reported in subjects in cohort 1. Overall, 4 fatal AEs were reported: death / progressive disease (N = 2), carcinoid syndrome (N = 1) and sepsis (N = 1). Conclusions: In PRRT-naïve subjects with SSTR+ unresectable or metastatic GEP-NETs treatment with up to 4 cycles of ²¹²Pb-DOTAMTATE (67.6 μCi/kg/cycle) was well-tolerated, with a safety profile consistent with the underlying disease and expected toxicities of radioligand therapy, similar to 177Lu-DOTATATE. The ORR of 47.2% in cohort 1 (50% in the pooled dataset) appears to be substantially higher than the ORR previously reported for 177Lu-DOTATATE in the pivotal NETTER-1 study (ORR 18% (10–25%)). Clinical trial information: NCT05153772 .

Understanding clonal heterogeneity and mechanisms of methotrexate resistance in two osteosarcoma PDX models.

e23512 Background: Osteosarcoma is a primary malignant bone tumor that is known to have significant intratumoral heterogeneity with branched cancer evolution. The lung is the most frequent site of metastatic disease and relapse occurs in more than 30 % children and young adults. It has been revealed that the metastatic ability and resistance of cancers including osteosarcoma might be due to the presence of a subset of cells within the intra-tumorally heterogeneous population. We investigated the emergence of resistant clonal subpopulations following targeted methotrexate treatment in two patient derived xenograft (PDX) models in vitro and in vivo. Our aim was to not only track the subclonal population of cells that establish in the lungs but also to identify clonal drivers and the mutational signature of the genes and pathways involved in MTX resistance. Methods: We previously established 20 barcoded osteosarcoma PDX models and demonstrated that the application of methotrexate (MTX-IC95) treatment as a selective pressure in seven models produces clonal subpopulations that were more resistant to MTX. In the current work we used barcoded next generation and RNA sequencing techniques to map the clonal and transcriptomic architecture of MTX resistant single clones in M36 and OS252 PDX models. We next injected the barcoded PDX cells intratibially in twenty severe combined immunodeficiency disease (SCID) mice to track the clonal population/subpopulation of cells that metastasize to the lungs. Following primary tumor growth, limb amputation was carried out and mice were treated with methotrexate or vehicle for two weeks. Primary tumor, blood and lung samples were collected after death from metastasis or euthanasia. All samples collected were snap frozen in liquid nitrogen and stored at -800C. DNA and RNA was extracted and analyzed by PCR, NGS or WES to map clonality, mutational and evolutionary profiles. Results: MTX treated single clones showed diversity and barcode abundance when compared to vehicle; barcode abundance reduced in the resistant clonal subpopulations when compared to the vehicles. Ten unique subclones were shared in both vehicle and MTX resistant clones in M36 while OS252 had only one shared subclone respectively. More than 50% of the injected mice developed primary tumors and matched lung micrometastases. We are currently analyzing both targeted and RNA sequencing results to further understand clonality, the mutational signature of the genes (DHFR, MTR, FPGS, GGH) and pathways involved in MTX resistance. Conclusions: We investigated mechanism of methotrexate resistance in two barcoded PDX models in vitro and in vivo using cytotoxicity, next generation and RNA sequencing techniques. Targeted amplicon sequencing of key genes involved in antifolate pathway will yield new information on clonal evolution and mechanisms of resistance.

Efficacy and safety of fruquintinib plus investigator's choice of chemotherapy as second-line therapy in metastatic colorectal cancer: Updated results of a multicenter, single-arm, phase 2 trial.

3571 Background: Fruquintinib, a potent and highly selective vascular endothelial growth factor receptor (VEGFR) inhibitor, combined with investigator’s choice of chemotherapy as second-line therapy in patients (pts) with metastatic colorectal cancer (mCRC) showed promising efficacy in preliminary analysis (2023 ASCO Poster-3582) of the prospective, open-label, multicenter, single-arm phase 2 trial (ChiCTR2200059280). Here we reported the updated efficacy data. Methods: Pts with mCRC progressed after first-line prior systemic treatment were administered fruquintinib (5~3 mg, d1-21, q4w) and investigator’s choice of chemotherapy (fluorouracil ± irinotecan ± oxaliplatin, d1, q3w) for up to 8 cycles. Patients without disease progression (PD) were followed by fruquintinib maintenance until PD or unacceptable toxicities. The primary endpoint was progression-free survival (PFS). The secondary endpoints included objective response rate (ORR), disease control rate (DCR), duration of response (DoR), overall survival (OS) and safety. Results: From November 2021 to November 2023, 100 pts were enrolled. Median age was 63 years (IQR, 56.5-71) and 61.0% were male. The left colon cancer involved in 77.0% pts. All pts had MSS/pMMR phenotype and 37.0% had RAS/BRAF-mutated tumors. 9.0% received prior anti-EGFR and 55.0% received anti-VEGF therapy. Most common sites of metastatic disease were liver (57.0%) and lung (41.0%). As of January 20, 2024, with a median follow-up of 9.3 mo, the median PFS was 6.9 mo (95%CI, 5.2-8.6), median OS was 20.1 mo (95%CI, 13.7-26.3). ORR was 26.0% (95%CI, 17.9-36.2), DoR was 11.3 mo (95%CI, 8.6-14.0), and DCR was 83.3% (95%CI, 74.0-89.9) in 96 efficacy-evaluable pts. The incidence of adverse events was comparable to the known toxicities associated with fruquintinib and chemotherapy. No treatment-related deaths occurred. Grade 3/4 adverse effects occurred in 33 pts (33.0%), and most commonly were neutropenia (21.0%), leukopenia (14.0%), thrombocytopenia (6.0%), proteinuria (5.0%), hypothyroidism (3.0%), diarrhea (2.0%), hand-foot syndrome (2.0%) and hypertension (1.0%). Conclusions: Fruquintinib combined with investigator’s chemotherapy followed by fruquintinib maintenance as second-line therapy showed satisfactory anti-tumor activity, prolonged PFS and OS, and manageable safety profiles in pts with mCRC. Further analysis of all pts with long-term follow-up will be presented in the future. Clinical trial information: ChiCTR2200059280.

Single institution retrospective review of patients with metastatic hormone receptor positive breast cancer receiving first line therapy of CDK4/6 inhibitors.

e13090 Background: Breast cancer continues to be the most commonly diagnosed cancer in women. The majority of these cancers are estrogen positive (ER+) and about 6% of new cases are stage 4 at time of diagnosis. The current standard of care for postmenopausal women with stage 4 ER+ breast cancer is a combination of an aromatase inhibitor (AI) with a cyclin-dependent kinase (CDK) 4/6 inhibitor. Based on Medicare data claim analysis from IQVIA, CDK 4/6 inhibitors are being used nationally in the first line setting in 56% of cases where 24% of cases were treated with AI monotherapy. The state of Kentucky currently lies below this national average by using this treatment regimen in 38% of cases where 47% of cases are treated with AI monotherapy. The reason for this discrepancy between the national average and Kentucky is currently unknown. To further understanding, we have conducted an internal review of adherence to the guidelines. Methods: This is a single center retrospective study done at University of Louisville, Brown Cancer Center. Data was collected on patients who had biopsy proven metastatic hormone positive breast cancer from July 2021 until May 2023 (n=41). Collected characteristics include age on diagnosis, tumor grade, sites of metastatic disease, first line treatment received, choice of CDK4/6 inhibitor if received, and prior exposure to chemotherapy or anti-estrogen therapy. Results: In our cohort of 41 patients, we found that 63.4% (n=26) of patients received an AI and CDK4/6 inhibitor in the first line. There were 4.88% (n=2) of patients who received AI monotherapy, 21.9% (n=9) received Fulvestrant and CDK4/6 inhibitor, 4.88 % (n=2) received AI and Fulvestrant and 4.88% (n=2) received Fulvestrant alone. In total, patients who received estrogen therapy plus CDK4/6 inhibitor totaled 85% of new patients (n=35). Conclusions: This internal review showed our institution to be compliant with endocrine therapy and CDK 4/6 inhibitor in front-line treatment for the majority of metastatic ER+ patients. Given the supportive data for use of CDK 4/6 inhibitors in front-line treatment, the compliance is expected to be much higher. We recommend continued discussion amongst oncology providers to help identify barriers to treatment and determine the causes for poor compliance in the state of Kentucky.

Correlation of previous local vaccination site “flares” during immunotherapy for metastatic melanoma with complete responses to therapy.

e21534 Background: mRNA vaccines have been shown to stimulate T-cells targeting patient-specific tumor neoantigens. When combined with immune checkpoint inhibitors (ICI) in a randomized Phase II trial, mRNA vaccines demonstrated improvement in recurrence free survival and distant metastasis free survival compared to ICI alone. We retrospectively examined patients (pts) with advanced melanoma treated more than 5 years ago on clinical trials with adjuvant NYESO1 or mRNA vaccine therapies (VT) then ICI upon recurrence and analyzed biomarkers correlating with treatment response. Methods: This retrospective study examined 22 pts with advanced melanoma treated between 2004-2017 with adjuvant vaccine therapies (VT). 10 of the 22 pts subsequently developed recurrent disease and were treated with ICI. We evaluated disease free interval following ICI, sex, age, BRAF status, HLA type, site of primary and metastatic disease, initial vaccine treatment, vaccine toxicities, stage and sites of melanoma recurrence, ICI treatment, response and toxicities, vaccine site flares or cutaneous immune related adverse events (irAEs) following ICI. Results: Of the 22 patients (11 male, 11 female) treated with adjuvant VT, median age at first vaccine was 53 years old. HLA type was known for 11 pts. Stage at initial VT was IIB to IIIC. 14 pts recurred following adjuvant VT. Median time from vaccine initiation to melanoma recurrence was 3.2 years (range 6.5 months to 11 years). 10 pts received ICI for recurrent melanoma, 3 pts received ipilimumab, 2 anti-PD1 monotherapy, 4 ipilimumab and nivolumab, and 1 nivolumab/relatlimab. Stage at first ICI was IIIB to IV M1d. 9 pts experienced cutaneous irAEs. 7 pts experienced local vaccine site flare reactions following ICI treatment. Additionally, 2 pts experienced vitiligo, 2 with dermatologic flares (bullous pemphigoid and psoriatic rash), 2 with generalized rash that resolved with steroid cream. 1 pt did not experience rash, vaccine site flare, nor irAE dermatologic flare. Of the pts who recurred, 2 pts had BRAF V600E mutations, and 1 of these pts experienced vaccine flare, the other did not. 1 pt with a BRAF Q16L mutation did not have vaccine flare. 6 out of 7 BRAF wild type pts who recurred and received ICI experienced a localized vaccine site flare. Median disease-free interval following ICI treatment was 1.5 years (range 3 months to 9 years). All 10 pts are disease-free and off ICI being closely monitored. Conclusions: Evidence of prior localized vaccination “flare” may be a biomarker for a complete immunologic response in pts with metastatic disease treated with immunotherapy. ICI targeting CTLA-4 and/or PD-1 both triggered this localized vaccination site response, suggesting that T cell memory and immunologic activation against melanoma antigens translate into clinical responses.

Hospital-treated infectious diseases, genetic susceptibility and risk of type 2 diabetes: A population-based longitudinal study

BackgroundThe longitudinal association between infectious diseases and the risk of type 2 diabetes (T2D) remains unclear. MethodsBased on the UK Biobank, the prospective cohort study included a total of 396,080 participants without diabetes at baseline. We determined the types and sites of infectious diseases and incident T2D using the International Classification of Diseases 10th Revision codes (ICD-10). Time-varying Cox proportional hazard model was used to assess the association. Infection burden was defined as the number of infection episodes over time and the number of co-occurring infections. Genetic risk score (GRS) for T2D consisted of 424 single nucleotide polymorphisms. ResultsDuring a median of 9.04 [IQR, 8.3–9.7] years of follow-up, hospital-treated infectious diseases were associated with a greater risk of T2D (adjusted HR [aHR] 1.54 [95 % CI 1.46–1.61]), with risk difference per 10,000 individuals equal to 154.1 [95 % CI 140.7–168.2]. The heightened risk persisted after 5 years following the index infection. Bacterial infection with sepsis had the strongest risk of T2D (aHR 2.95 [95 % CI 2.53–3.44]) among different infection types. For site-specific analysis, bloodstream infections posed the greatest risk (3.01 [95 % CI 2.60–3.48]). A dose-response association was observed between infection burden and T2D risk within each GRS tertile (p-trend <0.001). High genetic risk and infection synergistically increased the T2D risk. ConclusionInfectious diseases were associated with an increased risk of subsequent T2D. The risk showed specificity according to types, sites, severity of infection and the period since infection occurred. A potential accumulative effect of infection was revealed.

A phase I/II, first-in-human study of VLS-1488, an oral KIF18A inhibitor, in patients with advanced cancer.

TPS3181 Background: Chromosomal instability (CIN) is a hallmark of cancer characterized by high rates of chromosomal segregation errors during mitosis. This creates structural and numerical changes to chromosomes, driving genetic heterogeneity and cancer evolution. KIF18A is a mitotic kinesin protein shown to be important for successful division of cancer cells with CIN but not required for mitosis in normal diploid cells. Pre-clinical studies demonstrated that treatment of chromosomally unstable cancer cells in vitro and in xenograft models (HCC15 and OVCAR-3) with a KIF18A inhibitor resulted in failure of chromosomal congression, mitotic arrest, cell death and dose-dependent inhibition of tumor growth. VLS-1488 is an oral small molecule inhibitor of KIF18A that is being examined in an open-label, phase I/II, first-in-human study evaluating the safety, tolerability, pharmacokinetics (PK) and preliminary anti-tumor activity in advanced solid tumors with high prevalence of CIN. Methods: Key eligibility criteria include specific histologically confirmed metastatic or advanced tumor types with at least one site of measurable disease per RECIST 1.1, adequate organ function, and mismatch repair proficient/microsatellite stable.Eligible tumor types include high grade serous ovarian/fallopian tube/primary peritoneal cancer, squamous non-small cell lung cancer, triple negative breast cancer, gastric adenocarcinoma, gastroesophageal cancer, esophageal cancer, colorectal adenocarcinoma, transitional cell carcinoma of bladder, head and neck squamous cell carcinoma, ovarian or uterine carcinosarcoma, and uterine serous carcinoma. Subjects will receive VLS-1488 monotherapy continuously for 28-day cycles once daily. The study consists of two parts, Dose Escalation and Dose Expansion. Utilizing a Bayesian Optimal Interval (BOIN) design, Dose Escalation will examine the safety and tolerability of VLS-1488 at various dose levels (DLs) to identify the Maximum Tolerated Dose (MTD) and to select DLs for Dose Expansion. Dose Expansion may commence after the MTD or DLs of interest are identified. Dose Expansion will examine the safety, tolerability, preliminary efficacy and preliminary drug-drug interaction (DDI) and food effect risk of VLS-1488 in selected tumor types. Subjects enrolled to specific tumor type cohorts may be randomized to DLs of interest. Enrollment to Dose Escalation began in September 2023 and is ongoing. Clinical trial information: NCT05902988 .

Randomized controlled, open-label, phase IIb/III study of lurbinectedin in combination with doxorubicin versus doxorubicin alone as first-line treatment in patients with metastatic leiomyosarcoma.

TPS11590 Background: Lurbinectedin (LUR) is a synthetic chemical entity structurally related to trabectedin that inhibits oncogenic transcription and is active in tumors addicted to transcription. Synergistic activity of the combination of LUR with Doxorubicin (DOX) was found in solid tumors. Preliminary results from two trials showed efficacy for LUR/DOX in anthracycline-naïve advanced Leiomyosarcoma (LMS) (1st or 2nd line) at different doses. In a phase 2 trial in soft tissue sarcoma (STS) patients (pts) (mostly with LMS: 12/20 pts), a combination of DOX 50 mg/m2 + LUR 2 mg/m2 Day (D)1 q3wk resulted in a response rate (RR) of 35% (4/7 LMS pts responding) and a disease control rate (DCR) at 24 wks of 40% (1). A phase 1b/2 trial in 10 advanced STS pts found a RR of 60% (5 were LMS, with 3 partial responses) treated at DOX 25 mg/m2 D1 or D1,D8 + LUR 3.2 mg/m2 D1 q3wk, (2). The promising results of these trials provide a rationale for further exploring this combination in a phase 2b/3 trial as first-line therapy for metastatic LMS (SaLuDo - NCT06088290). Methods: SaLuDo is a randomized, open-label study evaluating LUR in combination with DOX compared to DOX alone as first-line treatment of pts with metastatic LMS. The primary endpoint is progression-free survival (PFS) according to Independent Radiological committee (IRC). Secondary endpoints include overall survival, PFS according to Investigator assessment (IA), overall response rate, duration of response, and clinical benefit rate (according to IRC and IA), safety profile, patient-reported outcomes, pharmacokinetics, and exploratory pharmacogenomic analysis. Main inclusion criteria include age ≥ 18 years, confirmed diagnosis of metastatic LMS, and no prior systemic treatment for metastatic disease. Exclusion criteria include prior treatment with anthracyclines, lurbinectedin or trabectedin. The phase 2b part of the study will randomize approximately 120 pts into 3 arms (1:1:1): Control arm (DOX 75 mg/m2 D1 q3wk; experimental ARM A (DOX 50 mg/m2 D1 + LUR 2.2 mg/m2 D1 + 1ry GCSF prophylaxis q3wk), and experimental ARM B (DOX 25 mg/m2 D1 + LUR 3.2mg/m2 D1 + 1ry GCSF prophylaxis q3wk). Stratification will be done according to site of primary tumor (uterine vs. soft tissue), sites of metastatic disease (lung as unique site vs. other) and time from diagnosis to study entry (≤ 12 months vs. &gt;12 months). One of the two experimental arms will be dropped out at the end of phase 2b. The study will then enter the phase 3 part and approximately 120 pts will be randomized 1:1 between the control arm and the selected experimental arm. An Independent Data Monitoring Committee will oversee the conduct of the study. The first patient was randomized in 09/2023. The phase 2b part of the study is ongoing and recruiting patients in Europe and the USA. 1. Cote EJC 2020; 126:21-32. 2. Cote. JCO 2023; 41: Abst 11507. Clinical trial information: NCT06088290 .

Association of quality of life (QoL) with mortality in patients with adenoid cystic carcinoma using an internationally validated QoL questionnaire (EQ-5D-5L): A new baseline.

6097 Background: An evaluation of impact on quality of life (QoL) is required for regulatory approval and reimbursement of new drug therapies. Almost all studies of new therapies in adenoid cystic carcinoma (ACC) are non-randomised with no comparator QoL measure. To support Health Technology Assessments and the evaluation of the clinical utility of these therapies, we sought to determine the QoL measures in a cohort of ACC patients and to assess for change over time and associations with clinical or prognostic factors. Methods: An internationally validated QoL questionnaire (EQ-5D-5L) was completed by ACC patients referred to an experimental medicine centre between 2019 and 2024, who provided written informed consent to analysis. EQ-5D value scores (EQV) were calculated from each questionnaire using the EuroQol England value set. A Cox proportional hazards model was built with EQV as a time dependent variable, with a variant using penalised smoothing splines to assess linearity. A base non-linear mixed effects (nlme) model was constructed between time and EQV. The relationship between EQV and other predictors (NOTCH1 alteration status, age at diagnosis, sex, local and/or metastatic recurrence, and primary site of disease) were tested against the base model using variant models built for each predictor. Both analyses used R Statistical Software (v4.3.2) with survival and nlme packages in Rstudio (v2023.12.0.0). Results: Between 2019 and 2023, 563 EQ-5D-5L questionnaires were completed by 161 patients with ACC (median 2 responses/patient, range 1 to 20). NOTCH1 alteration was seen in 8% (13/161), median age at diagnosis 49 years (range 17 to 81), 40% male, 36% (58/161) had a major salivary gland as primary site, and 14% had local recurrence, 46% metastatic recurrence and 26% both for 86% total with recurrent disease (139/161). For all 161 patients, median EQV was 0.81 (range -0.22 to 1.0); an EQV of 1 is ideal QoL and 0 is QoL as bad as death. The median EQV for the clinical subgroups were 0.83 (NOTCH1, IQR 0.74-0.87), 0.84 (no recurrence, IQR 0.75-0.92), 0.80 (local recurrence only, IQR 0.70-0.86), 0.81 (distant metastasis only, IQR 0.70-0.92), 0.83 (distant and local, IQR 0.75-0.92), 0.84 (major primary site, IQR 0.75-0.92), 0.81 (other primary site, IQR 0.70-0.89), and no statistical differences were identified between these groups. However, a decrease in EQV from 1 to 0 was associated with an eightfold increase in risk of death in the total population (HR= 0.118, 95% CI 0.057 to 0.244, p= &lt;0.001). There was a significant non-linear relationship between EQV and survival over time (p=0.011), with a greater marginal effect on survival for EQVs &gt;0.81. Conclusions: For patients with ACC, a worse QoL as measured by EQ-5D-5L was associated with a significantly increased risk of death. NOTCH1 and disease recurrence were not associated with a worse QoL.

Inherited Germline Variants in Urinary Tract Cancer: A Multicenter Whole-Exome Sequencing Analysis and Correlation With Clinical Features and Tumor Genomics.

This study investigates a real-world multicenter cohort of patients with urinary tract cancer (UTC), with primary disease sites including the bladder, urethra, and upper tract, who enrolled for research molecular testing of their germline and tumor. The purpose of this study was to evaluate factors that could affect the likelihood of identifying a clinically actionable germline pathogenic variant (PV). Patients with UTC were identified from 10 cancer institutes of the Oncology Research Information Exchange Network consortium. The data set comprised abstracted clinical data with germline and tumor genomic data, and comparative analyses were conducted. Clinically actionable germline PVs in cancer predisposition genes were identified in 16 (4.5%) of 354 patients. A higher proportion of patients with the urethra and the upper tract as the primary sites of disease had PVs with a prevalence of 11% (5/45), compared with only 3.6% (11/308) in those with the bladder as the primary site of disease (P = .04). There were no significant differences in markers of genomic instability (such as tumor mutational burden, microsatellite instability [MSI], and loss of heterozygosity, copy number, and chromosomal instability) between those with PVs and those without (P > .05). Of the PVs identified, 10 (62%) were in homologous recombination repair (HRR) genes, three (19%) in mismatch repair (MMR) genes, and three (19%) in genes associated with other pathways. Tissue-based assessment of genomic instability, such as MSI, does not reliably indicate germline PV. A comprehensive clinical germline testing approach that includes HRR genes in addition to MMR genes is likely to yield PVs in approximately one of 10 patients with nonbladder primary disease sites such as the upper tract and the urethra.

Safety and efficacy of osimertinib plus consolidative stereotactic ablative radiation (SABR) in advanced EGFR mutant non-small cell lung cancer (NSCLC): Results from a multi-center phase II trial.

8518 Background: Despite high response rates to EGFR inhibitors, patients with advanced EGFR mutant NSCLC generally experience disease progression within two years (osimertinib median PFS 18.9 months, median OS 38.6 months). We sought to determine whether administration of SABR to residual sites of disease at the time of expected best response to EGFR inhibition could prolong disease control. Methods: This was a multi-center single-arm phase 2 study. Eligible patients had advanced EGFR mutant (exon 19 or 21) NSCLC not restricted by number, site, or size of metastases; ECOG 0-2; no prior treatment with EGFR inhibitors or immune checkpoint inhibitors; and no history of interstitial lung disease. Patients with stable or responding disease after 8 weeks of osimertinib received SABR to persisting lesions, followed by continued osimertinib until progression or intolerance. At subsequent progression, patients could receive further SABR and continue osimertinib if deemed clinically feasible and appropriate. The primary endpoint was progression-free survival (PFS); secondary endpoints included duration on osimertinib, toxicity, and overall survival (OS). Results: A total of 43 patients (32 women, 11 men) were enrolled and initiated osimertinib, of whom 29 (67%) received SABR. Reasons SABR was not administered included inadequate response (9%), insufficient residual disease (19%), and other (5%). At a median follow-up of 35.7 months (95% CI, 28.8, 37.6), 42 evaluable patients had a median PFS of 32.6 months and a median OS of 45.7 months. The median duration of osimertinib was 31.5 months. Grade ≥3 toxicities included one incidence each (2%) of the following: pain at the site of radiation, paronychia, liver enzyme elevation, fatigue, hyponatremia, diarrhea, and pneumonitis. Conclusions: Osimertinib plus consolidative SABR appears to provide a PFS and OS benefit when considered against historical data with osimertinib alone. This treatment strategy may offer a well-tolerated and practical approach to improving outcomes for patients with advanced EGFR mutant NSCLC. Clinical trial information: NCT03667820 .

Chemotherapy in the last 30 days of life, correlation with age and palliative care referral: A 1-year retrospective gastrointestinal program experience at SQCCCRC.

e24038 Background: Chemotherapy in the last days of life can carry unnecessary toxicities to the patient with no significant impact on survival and disease outcome. This is becoming of greater interest with the involvement of palliative care in patient’s management along with the advent of new therapeutic options with progressively increased cost of treatment. Methods: In our retrospective study, we aimed to analyze retrospectively the data of GI tumors treated at SQCCCRC over one year, by looking at the possible factors influencing the time from last treatment to death. We conducted chart review of all death that occurred between January 2023 and December 2023 in the GI cancer program at SQCCCRC. Information on demographics, type of GI cancer, type, intent and route of chemotherapy, line of chemotherapy and referral to palliative care were collected. Results: A total of 65 patients died within the GI cancer program between January 1st, 2023, to dec 31st, 2023. Most (72.7%) of the patients died of disease progression. Intent for chemotherapy was palliative in 90.9% of cases. Chemotherapy was parenteral (Intravenous) for the majority (60%, 38/63) of the patients. From all the recovered deaths, a total of 52 patients (82%) were referred to palliative team before death whereas palliative team was involved in the journey of all patients. 12 deaths out of 65 occurred in ICU. Only 11 out of 65 patients died within last 30 days of treatment: 81.8% of them were under palliative care at the time of death. For this group, the median age at diagnosis was 50 yo. Median age at death was 61 yo. 72.7% were male. Primary site of disease was colon followed by stomach. Median time from diagnosis to palliative referral was 13.5 months. 8 patients died within 3.5 days of referral to palliative care. In the logistic regression models, only age at diagnosis was a significant predictor for receiving chemotherapy in the last 30 days of life (p = 0.019). Older age was associated with lower odds of receiving chemotherapy in this period (OR = 0.94, 95% CI = 0.89-0.99). Referral to palliative chemotherapy was not associated with decreased rate of treatment administration within last 30 days of life. Conclusions: While some real-world data suggested correlation between shifting to palliative care and administration of chemotherapy in the last 30 days of life, this was not the case in our collected sample, and only the age of the patient played a role in the chemotherapy timing before death. Further studies are needed to study the reasons behind and the best way to improve patient’s centered approach.

Scintigraphy of Gastrointestinal Motility: Best Practices in Assessment of Gastric and Bowel Transit in Adults.

Various radiologic examinations and other diagnostic tools exist for evaluating gastrointestinal diseases. When symptoms of gastrointestinal disease persist and no underlying anatomic or structural abnormality is identified, the diagnosis of functional gastrointestinal disorder is frequently applied. Given its physiologic and quantitative nature, scintigraphy often plays a central role in the diagnosis and treatment of patients with suspected functional gastrointestinal disorder. Most frequently, after functional gallbladder disease is excluded, gastric emptying scintigraphy (GES) is considered the next step in evaluating patients with suspected gastric motility disorder who present with upper gastrointestinal symptoms such as dyspepsia or bloating. GES is the standard modality for detecting delayed gastric emptying (gastroparesis) and the less commonly encountered clinical entity, gastric dumping syndrome. Additionally, GES can be used to assess abnormalities of intragastric distribution, suggesting specific disorders such as impaired fundal accommodation or antral dysfunction, as well as to evaluate gastric emptying of liquid. More recently, scintigraphic examinations for evaluating small bowel and large bowel transit have been developed and validated for routine diagnostic use. These can be performed individually or as part of a comprehensive whole-gut transit evaluation. Such scintigraphic examinations are of particular importance because clinical assessment of suspected functional gastrointestinal disorder frequently fails to accurately localize the site of disease, and those patients may have motility disorders involving multiple portions of the gastrointestinal tract. The authors comprehensively review the current practice of gastrointestinal transit scintigraphy, with diseases and best imaging practices illustrated by means of case review. ©RSNA, 2024 See the invited commentary by Maurer and Parkman in this issue.

Demographic and socioeconomic analysis of patients with glucagonoma: Insights from the National Cancer Database.

e16319 Background: Glucagonoma is a rare glucagon-producing alpha islet cell tumor primarily of the pancreas, and a type of pancreatic neuroendocrine tumor. These types of cancers have a 10-year survival rate of about 38%. Metastasis may be found in approximately 50% of glucagonoma cases. As a result of the low incidence of glucagonoma, analysis of the diagnostic patterns may provide more insight into the disease’s epidemiology. This study analyzed the National Cancer Database (NCDB) to examine demographic factors of individuals diagnosed with glucagonoma. Methods: ICD-8152-3 Data from the NCDB between 2004-2020 was gathered to perform a retrospective cohort analysis on patients diagnosed with glucagonoma (N = 88). Descriptive statistics were used to investigate demographic factors such as age, sex, race, Hispanic status, years of education, insurance, facility type, distance from facility, and Charlson-Deyo score. Regression analysis was utilized to evaluate incidence trends. Results: We found that patients had an average age of 61 years (SD = 13, range = 23-90), with an average tumor size of 53 mm (SD = 39, range = 12-140), and the majority were male (61%) and White (90%). The majority of patients (97%) did not receive palliative care, with surgery (57%) and chemotherapy (28%) being the primary treatments. Post-surgery, 90% had no residual tumor, and survival rates were 98% after thirty days and 96% after ninety days. Most were treated in academic/research facilities (43%) and had private insurance (59%) or Medicare (34%). The largest median household income quartile of these patients was $74,063 or more (39%).The study noted a 2-year survival rate of 74%, a 5-year rate of 54%, and a 10-year rate of 31%, with a mean survival of 89.3 months. The primary disease sites were the tail of the pancreas (32%) and pancreas, NOS (22%). The distribution across NCDB Analytic Stage Groups was 19% for Stage I, 11% for Stage II, 2% for Stage III, and 23% for Stage IV. Conclusions: This study represents the first analysis of glucagonoma patients using the National Cancer Database, filling a gap in our understanding of the disease. The findings indicate that the majority of glucagonoma patients were non-Hispanic, White, and had tumors primarily located in the tail of the pancreas, aligning with earlier case report descriptions. Socioeconomically, patients most likely had earnings above the median income quartile, resided in densely populated metropolitan areas, and received treatment in academic facilities. Further investigation is necessary to have a more thorough grasp of the impact of demographic and socioeconomic characteristics on glucagonoma patients' diagnosis, course of treatment, and overall survival rates.