Survival Outcomes Research Articles

Etiologically Significant microRNAs in Hepatitis B Virus-Induced Hepatocellular Carcinoma.

Hepatitis B virus (HBV) infection has been causally linked to hepatocellular carcinoma (HCC) in more than 50% cases. MicroRNAs (miRNAs) play cross-cutting mechanistic roles in the complex interplay between viral pathogenesis, host survival, and clinical outcomes. The present study set out to identify etiologically significant human miRNAs associated with HBV infection in liver-related pathologies leading to HCC. In diverse tissue types, we assembled 573 miRNAs differentially expressed in HBV-associated liver pathologies, HBV infection, fibrosis, cirrhosis, acute on chronic liver failure, and HCC. Importantly, 43 human differentially expressed miRNAs (hDEmiRs) were regulated in serum/plasma and liver tissue of patients with HBV-positive conditions. However, only two hDEmiRs, hsa-miR-21-5p and hsa-miR-143-3p, were regulated across all disease conditions. To shortlist the functional miRNAs in HBV-induced HCC pathogenesis, a reverse bioinformatics analysis was performed using eight GEO datasets and the TCGA database containing the list of differentially regulated mRNAs in HCC. A comparative study using these data with the identified targets of hDEmiRs, a set of unidirectionally regulated hDEmiRs with the potential to modulate mRNAs in HCC, were found. Moreover, our study identified five miRNAs; hsa-miR-98-5p, hsa-miR-193b-3p, hsa-miR-142-5p, hsa-miR-522-5p, and hsa-miR-370-3p targeting PIGC, KNTC1, CSTF2, SLC41A2, and RAB17, respectively, in HCC. These hDEmiRs and their targets could be pivotal in HBV infection and subsequent liver pathologies modulating HCC clinical progression. HBV infection is the largest contributor to HCC, and the present study comprises the first of its kind compendium of hDEmiRs related to HBV-related pathologies.

Outcomes of patients with metastatic solid cancers treated on early phase clinical trials in western Australia.

e23094 Background: Cancer drug development is flourishing with novel immunotherapy combinations, antibody drug conjugates and increasingly molecularly targeted therapies that have pushed the inclusion of phase I clinical trials into earlier lines of systemic treatment. Linear Clinical Research is a dedicated Phase I centre with a catchment area of over 3 million people. We conducted a retrospective review into the outcomes of our centre. Methods: We included patients between 01/01/2020 to 30/04/2023, with advanced/metastatic or rare cancers with no available or suitable standard of care treatment. Data were extracted from our internal database with minimum follow up of 6 months. The primary endpoint was overall survival (OS). Other endpoints included progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), time to response (TTR), duration of response (DOR), duration of treatment (DOT), post-treatment survival (PTS), and 90-day mortality. Subgroup analyses based on treatment type were performed. Multivariate cox regression analysis was performed as part of tertiary endpoints. Results: 251 patients were recruited to 53 trials. Median age : 61 years (range: 21-83 years), 54.6% female, 74.1% Caucasian, ECOG 0-1: 90.8%, 26.7% rare cancers, 52.2% had 0-1 line of previous treatment, 47.8% had ≥ 2 lines. Trial treatments were: 51.4% immunotherapy (IO), 30.7% targeted therapy matched to molecular findings (TT), 2.8% antibody drug conjugate (ADC), 12.7% combination therapy (IO/TT/ADC/chemotherapy), 2.0% endocrine therapy alone, and < 1% chemotherapy. At data cut-off, 129 OS events had occurred (56.0%, median follow up of 22.0 months).The median OS was 16.0 months (95% CI 11.1 - 20.9), median PFS: 3.0 months (95% CI 2.2 - 3.8), ORR: 23.6%, DCR: 67.3%, median TTR: 2.0 months (IQR: 1.0-3.0), median DOR: 14.0 months (IQR: 6.0-38.0), median DOT: 3.0 months (IQR 1.0-10.0), median PTS: 7.0 months (IQR 2.0-27.0), 90-day mortality: 17.7%. Median OS based on treatment type: 11.0 months (95% CI 5.7-16.3) (IO), 12.0 months (95% CI 1.6-22.4) (TT), median not reached (range :1.0-28.0) (ADC), and 19.0 months (95% CI 13.6-24.4) (combination therapy). Median PFS based on treatment type: 2.0 months (95% CI 1.2-2.8) (IO), 5.0 months (95% CI 2.5-7.5) (TT), 10.0 months (95% CI: 0.0-28.0) (ADC), 6.0 months (95% CI 2.2 - 9.8) (combination therapy). Multivariate Cox analysis showed that higher number of lines of previous treatment was negatively associated with PFS and OS when adjusted for age, gender, type of treatment, and baseline sum of diameter (SOD). Conclusions: Our overall OS, ORR, and DCR are better than historical data of phase 1 during chemotherapy era , and are comparable to other centers nationally and internationally. Further work needs to be done to improve survival outcomes including algorithms to better match patients and trials earlier in their disease course.

Automated digital oncologic data review for breast cancer research: AI-enabled mCODE and field-of-interest extraction framework.

e12647 Background: Enhancing outcomes in cancer care and research can be optimally achieved by accelerating data extraction from unstructured electronic health resources. Understanding the association between treatment response markers and long-term outcomes is crucial for refining cancer therapeutic approaches and improving patient prognosis. In this study, we explore the association of oncologic outcomes with pathologic complete response (pCR) in high-risk early-stage breast cancer treated with neoadjuvant chemotherapy (NACT) using automated oncologic data extraction framework. Methods: Patients with primary stage I-III breast cancer who received NACT followed by mastectomy, with or without immediate breast reconstruction from January 2010 to August 2023 were retrospectively analyzed. We extracted pCR results and data on clinical and pathological stage, tumor subtype, grade, and treatment regimens and factors affecting postoperative complications from electronic medical records based on the AI enabled-mCODE (Minimal Common Oncology Data Elements) and fields of interest extraction framework. Employing mixed-effects Cox models, we explored the association between pCR and event-free survival (EFS), distant recurrence free Survival (DRFS) and overall survival (OS). Survival curves of patients were estimated using Kaplan-Meier method. Multivariate analysis was performed to evaluate the predictive factors for pCR. Results: Overall, 2725 patients were analyzed. The median age was 50.6 years. The median follow-up was 67 months. pCR was achieved in 31.0%. Hazard ratio for pCR vs. non-pCR were 0.34 for EFS (95% CI, 0.25-0.45), 0.32 for DRFS (95% CI, 0.23-0.43), 0.21 for OS (95% CI, 0.13-0.34), varying from 0.13 to 0.56 for EFS, 0.12 to 0.48 for DRFS and 0.07 to 0.40 for OS. The presence of pCR remained prognostic for event-free survival in multivariate models adjusted for age, tumor size, and nodal status at baseline. Conclusions: This study confirms that patients achieving pCR after NACT have better long-term survival outcomes that patients who do not. Oncologic data extraction from unstructured electronic medical records using AI-enabled extraction framework can be expected to enhance robust cancer research and generate valuable insights from real-world practice settings for tailored therapeutic decision-making. [Table: see text]

Long-term prognosis of patients with gallbladder carcinoma after curative-intent resection based on changes in the ratio of carbohydrate antigen 19-9 to total bilirubin (CA19-9/TB): a multicenter retrospective cohort study.

The prognostic value of carbohydrate antigen 19-9 (CA19-9) is known to be affected by elevated bilirubin levels in patients with gallbladder carcinoma (GBC). The clinical significance of changes in the ratio of CA19-9 levels to total bilirubin (TB) levels in patients with GBC after curative-intent resection remains unknown. The aim of this study was to determine the prognostic value of changes in preoperative and postoperative CA19-9/TB ratio in these patients. Prospectively colleced data on consecutive patients who underwent curative-intent resection for GBC between January 2015 and December 2020 stored in a multicenter database from 10 hospitals were analysed in this retrospective cohort study. Based on the adjusted CA19-9 defined as the ratio of CA19-9 to TB, and using 2×103 U/µmol as the upper normal value, patients were divided into a normal group (with normal preoperative and postoperative adjusted CA19-9), a normalization group (with abnormal preoperative but normal postoperative adjusted CA19-9), and a non-normalization group (with abnormal postoperative adjusted CA19-9). The primary outcomes were overall survival (OS) and recurrence-free survival (RFS). The log-rank test was used to compare OS and RFS among the groups. The Cox regression model was used to determine factors independently associated with OS and RFS. The normal group (n=179 patients) and the normalization group (n=73 patients) had better OS and RFS than the non-normalization group (n=65 patients) (the 3-year OS rates 72.0%, 58.4% and 24.2%, respectively; the RFS rates 54.5%, 25.5% and 11.8%, respectively; both P<0.001). There were no significant differences between the normal and the normalization groups in OS and RFS (OS, P=0.255; RFS, P=0.130). Cox regression analysis confirmed that the non-normalization group was independently associated with worse OS and RFS. Subgroup analysis revealed that the non-normalization group of patients who received adjuvant therapy had significantly improved OS and RFS as compared to those who did not receive adjuvant therapy (OS, P=0.025; RFS, P=0.003). Patients with GBC who underwent curative-intent surgical resection with postoperative abnormal levels of adjusted CA19-9 (the CA19-9/TB ratio) were associated with poorer long-term survival outcomes. Adjuvant therapy after surgery improved the long-term outcomes of these patients.

Three-year disease-free survival after transanal vs. laparoscopic total mesorectal excision for rectal cancer (TaLaR): A randomized clinical trial.

3516 Background: Transanal total mesorectal excision (taTME) has gained significant traction as an effective approach for treating rectal cancer. Many previous studies reported positive relevant short-term results, histopathological results and associated complications of taTME compared to laparoscopic total mesorectal excision (laTME). Nonetheless, long-term oncological outcomes of taTME remain controversial. This study aimed to compare the 3-year DFS of taTME with laTME. Methods: We conducted a phase 3, randomized, open-label, noninferiority trial to compare the survival outcomes of taTME versus laTME in patients with rectal cancer located below the peritoneal reflection. This trial encompassed 16 hospitals across 10 provinces in China, with a total enrollment of 1,115 patients. We set the 3-year disease-free survival (DFS) and 5-year overall survival (OS) as the primary endpoints for analysis. The analysis of the 3-year DFS was conducted following a predefined modified intention-to-treat principle. This study is registered with ClinicalTrials.gov, number NCT02966483. Results: The taTME group exhibited a 3-year DFS rate of 83.42%, and the laTME group achieved a 3-year DFS rate of 82.86%. The marginal difference of 0.56% between the DFS rates of the two groups (97.5% CI, −4.83 to 5.95, P &lt; 0.0001 for noninferiority) suggests comparable outcomes. Moreover, the rates of local recurrence were 3.90% in the taTME group and 3.62% in the laTME group, indicating similar degrees of localized tumor control. Regarding overall survival, the taTME group demonstrated a rate of 94.50% compared to 92.01% in the laTME group. In the taTME group, patients who are male or underwent neoadjuvant showed a higher 3-year OS than that in the laTME group. Conclusions: In patients with mid-low rectal cancer, the 3-year DFS of taTME is not inferior to that of laTME. This study provides evidence supporting the clinical effectiveness of taTME in the treatment of rectal cancer. Clinical trial information: NCT02966483 .

Quality-adjusted time without symptoms of disease or toxicity (Q-TWiST) analysis of fruquintinib + best supportive care (BSC) compared with placebo + BSC in metastatic colorectal cancer (mCRC): Results from the FRESCO-2 trial.

e15554 Background: As mCRC and its treatment can adversely impact quality of life (QoL), maintaining QoL is an important treatment goal in addition to improving survival outcomes, particularly as patients progress through lines of therapy. In the global, randomized, double-blind, phase 3 FRESCO-2 trial (NCT04322539), fruquintinib (F) + BSC vs placebo (P) + BSC demonstrated significantly improved overall survival (OS) (median 7.4 months vs 4.8 months; HR 0.66, 95% confidence interval [CI] 0.55–0.80) and progression-free survival, with a manageable safety profile and without deterioration of QoL in heavily pretreated patients with refractory mCRC. The objective of this post-hoc Q-TWiST analysis was to assess the quality-adjusted survival benefit of F + BSC in the context of the FRESCO-2 trial. Methods: The Q-TWiST analysis was applied to all 691 randomized patients from FRESCO-2 (F + BSC n = 461 vs P + BSC n = 230). Survival time of each patient was partitioned into 3 health states: time spent with treatment-emergent adverse events of CTCAE grade 3 or 4 before disease progression (TOX), time before disease progression without toxicity (TWiST), and time between disease progression and death or censoring (REL). Assuming utility coefficients of 1 for TWIST and 0.5 for TOX and REL, Q-TWiST was calculated as the utility-weighted sum of the time spent in each health state. The mean time spent in each of the 3 health states was calculated for each treatment group using Kaplan-Meier analysis, and a 95% CI for the difference between treatment was calculated using the nonparametric bootstrap method. Results: Q-TWiST was 6.25 months for F + BSC and 4.21 months for P + BSC, a difference of 2.04 (95% CI 1.51–2.57) months longer with F + BSC vs P + BSC. This difference in Q-TWiST was mainly driven by the difference in the TWiST component (2.14 months [95% CI 1.78–2.49]; F + BSC 4.06 months vs P + BSC 1.92 months). The relative Q-TWiST gain, calculated as the difference in Q-TWiST divided by the mean OS time of the P + BSC group, was 31.4% in favor of F + BSC. Conclusions: In the FRESCO-2 trial, F + BSC demonstrated a clinically meaningful quality-adjusted survival benefit compared with P + BSC in heavily pretreated patients with refractory mCRC. Clinical trial information: NCT04322539 .

The relationship between cardiometabolic abnormalities and mortality among women with and without cancer in the Women’s Health Initiative (WHI).

e24007 Background: Prior studies of women with obesity-associated cancers in the Women’s Health Initiative (WHI) showed higher overall and mortality due to cardiovascular disease (CVD) for women with a higher number of cardiometabolic risk factors at baseline. It is unclear if this risk differs from women without cancer. In order to determine if this relationship differs among both groups, we compared the association between cardiometabolic risk factors and mortality among women in the WHI with and without cancer. Methods: Women with one of five early-stage obesity-associated cancers (breast, colorectal, endometrial, ovarian, non-Hodgkin lymphoma), and matched controls without history of cancer, were selected from the WHI-Life and Longevity After Cancer (LILAC) study. Cardiometabolic risk factors included high waist circumference (WC) (≥88 cm), systemic hypertension ( &gt; 130/85 mm Hg) measured at study visits, and self-reported history of diabetes and elevated cholesterol. Multivariable Cox proportional hazards models (all-cause mortality) and Fine-Gray models (CVD and non-CVD mortality) were used to calculate hazard ratios (HR) and 95% confidence intervals (CI) to evaluate the association between baseline cardiometabolic risk factors and survival outcomes for the cancer and non-cancer cohorts in separate models. Sensitivity analyses included women in the cancer-cohort who received cardiotoxic chemotherapy. Results: A total of 7,491 and 35,508 women were analyzed in the cancer and non-cancer cohorts respectively. CVD was the most common cause of death (excluding cancer) in both non-cancer (41.4%) and cancer (41.5%) cohorts. Adjusted Cox models showed that the proportion of deaths due to any cause, by number of cardiometabolic risk factors, was significantly higher in the non-cancer compared to the cancer cohort (p-value = 0.02), with the HR values being higher for those with 3-4 risk factors compared to 1-2. Similar results were seen for each individual risk factor except for WC. Regarding CVD and non-CVD mortality, in competing risks models, there were no significant differences in the risk of death by number of risk factors, between the cancer and non-cancer cohorts (p = 0.21 and 0.22) respectively. Sensitivity analyses for women who received a cardiotoxic regimen, (81.5% anthracyclines alone, 13.4% anti-HER2 alone, and 5.1% both) showed no differences in the results for all-cause mortality, and CVD mortality. However, for non-CVD mortality, the proportion of deaths was significantly higher for women in the non-cancer cohort (p = 0.03). Conclusions: Cardiometabolic risk factors had a greater impact on mortality among women without cancer compared to those with cancer, except for death due to CVD which was similar between groups, suggesting that CVD risk reducing interventions are of equal importance for women with and without cancer.

Using an artificial intelligence platform to enhance cancer detection rates in primary care.

1560 Background: Patients with cancer who are diagnosed in a primary care setting have the best survival outcomes compared to any other route (e.g. Emergency department, routine referrals, incidental findings etc). This is primarily attributed to detection of cancer at an early stage. In the UK, the Cancer Detection Rate (CDR) metric serves as a measure of this, representing the percentage of cancer diagnoses originating from primary care referral routes. However, detecting cancer presents significant challenges, primarily due to the non-specific nature of cancer presentations, their tendency to overlap with symptoms of other conditions, and their relatively low prevalence. Artificial intelligence (AI) platforms may be able to support this endeavor but are yet to be established. C the Signs is an AI-enabled clinical decision support tool integrated into primary care practices to help clinicians stratify the risk of cancer and advise on which cancer pathway is most appropriate (if at all) for the patient’s presentation and history. Methods: An observational cohort study was undertaken between 1st May 2021 and 31st March 2022 where 35 practices (covering a population of almost 420,000) within the same geographic region in the East of England were offered the use of C the Signs, with the practices opting out as controls. All practices had the same access to referral and cancer diagnostic pathways within the region. The primary end point was to identify if C the Signs had a statistical impact on cancer detection rates in primary care through nationally linked data via Public Health England. Results: In practices utilizing C the Signs the CDR significantly increased from 58.7% in 2020-21 (prior to the implementation of C the Signs) to 66.0% in 2021-22, reflecting a significant increase of 12.3% (p &lt;0.05). In contrast, practices not using C the Signs maintained a stable CDR of 58.4% in both years. There was no statistically significant variance observed in the referral rate between the two groups, indicating no notable increase in diagnostic or referral activities. Conclusions: These findings underscore the importance of integrating cutting-edge technologies into primary care to improve cancer detection rates and facilitate early-stage diagnosis. Implementation of such advancements holds promise for reducing cancer-related mortality rates and enhancing overall patient outcomes.

Profile of breast cancer in patients with Li-Fraumeni syndrome: An institutional experience.

e13042 Background: Li Fraumeni syndrome (LFS) is a rare autosomal dominant syndrome, associated with multisystem cancer predisposition. Considering the rarity of this syndrome, studies are very sparse on survival outcomes of breast cancer with germline TP53 mutation and there exists discrepancy amongst the results. Methods: This retrospective observational study included 17 patients with germline TP53 mutated breast cancer registered at All India Institute of Medical Sciences (AIIMS), New Delhi, India between the period of 1st April 2016 to 31st Dec 2023. Among the 577 high-risk breast cancer patients, who underwent germline mutation testing, 231 (40.03%) cases had pathogenic mutation [145(25.12%) were BRCA mutated,15 (2.59%) were TP53 mutated, and the rest were others pathogenic variant]. All the TP53 mutations were crosschecked via the ClinVar mutation database to be classified as pathogenic. Results: The median age of 15 patients was 31 years (23-55) and 12 (80%) cases were premenopausal. All the patients had breast cancer as the index malignancy. The Stage distribution (AJCC-7th edition) Stage I, 1(6.6%); Stage II, 7 (46.6 %); Stage III, 4 (26.6 %); and Stage IV, 3 (20 %). Eight cases (53.3%) were HER2 positive, 4 (26.6%) were hormone receptor-positive, and 3 (20%) were Triple-negative breast carcinoma (TNBC). Ten (10) patients received neoadjuvant chemotherapy and 6 (60%) had a complete pathological response. Eight cases (53.3%) cases had a significant family history with 9 (60%) of them having at least one first-degree relative with cancer and two had more than one first-degree relative with cancer. One patient had a family history of LFS. The most common familial cancer was breast, followed by lung, GI malignancies, brain tumor, and sarcoma. Synchronous breast cancer was seen in 2 patients, synchronous malignancies were seen in 4 cases (one patient: each with lung adenocarcinoma, periampullary carcinoma, carcinoma colon, and synovial sarcoma, along with breast cancer), Four patients (26.6%) had metachronous cancers: lung cancer, ovarian carcinoma, contralateral breast cancer, and high-grade sarcoma respectively. The most common mutations were point mutations ( n = 11, 73.3%) followed by frameshift mutations ( n = 4, 26.6%). The subtypes of point mutations included missense mutations ( n = 9) and nonsense mutations ( n = 2) with the most common aberration being a replacement of arginine with glycine (c.743G&gt;A, p. Arg248Gln) and locus being exon 7. The median disease-free survival was 41 months and progression-free survival was 15 months. Conclusions: The prevalence of TP53 mutation in our breast cancer patients is 2.5%. With standard treatment protocols, the overall survival of LFS-associated breast cancer is similar to the historic cohort of patients without any germline mutation. Active surveillance of the patient and family screening is imperative, for all positive cases.

Multimodal fully automated predictive model for therapeutic efficacy of first-line cancer immunotherapy based on clinical information and imaging modalities including brain MRI and chest CT images in advanced non-small cell lung cancer.

1555 Background: The integration of imaging and clinical data through artificial intelligence (AI) holds promise for more accurately predicting the therapeutic efficacy of immune checkpoint inhibitors (ICI) ± platinum-based chemotherapy in individual patients with advanced non-small cell lung cancer (NSCLC). However, tumor segmentation still relies entirely on radiologist evaluation and has not yet achieved fully automated tumor evaluation for image analysis. Furthermore, while central nervous system (CNS) metastasis is a critical prognostic factor in patients with advanced NSCLC, radiomics has primarily focused on chest imaging, with few studies incorporating brain MRI analysis. Methods: This study included patients with advanced NSCLC treated with ICI ± platinum-based chemotherapy as first-line therapy from March 2017 to August 2023. We developed an ensemble model combining a logistic regression model that analyzes clinical information with a deep learning model that extracts image features. Each sub-model was independent, allowing for individual adjustments and the ability to be attached or detached. Both models were trained to predict response, 12-month progression-free survival (PFS), and 12-month overall survival (OS) using cross-entropy loss. The dataset was randomly divided into training, validation, and test sets in a 5:3:2 ratio. This random assignment was repeated four times, and the average area under the curve (AUC) was calculated. The test sets were further classified into high- and low-risk groups based on the predicted results, and log-rank tests were performed on their survival curves. Results: The study included 232 patients, with 89 (38%) receiving ICI alone and 143 (62%) receiving ICI + platinum-based chemotherapy. In the entire population, the overall response rate (ORR) for ICI ± platinum-based chemotherapy was 49.5%, with a median PFS of 7.1 months (95% confidence interval [CI]: 5.8-9.1) and a median OS of 24.5 months (95% CI: 21.2-30.3). The model achieved an AUC of 0.70 (95% CI: 0.65- 0.76) for predicting response, 0.65 (95% CI: 0.59-0.71) for 12-month PFS, and 0.69 (95% CI: 0.48-0.90) for 12-month OS. Test sets were classified into high-risk (N = 55) and low-risk (N = 60) groups. The median PFS was 6.8 months in the high-risk group and 14.7 months in the low-risk group (p &lt; 0.05). The median OS was 21.5 months in the high-risk group and 34.3 months in the low-risk group (p &lt; 0.05). Conclusions: We have demonstrated that a multimodal, fully automated ensemble model has significant predictive accuracy for the efficacy and survival outcomes of ICI ± platinum-based chemotherapy in patients with advanced NSCLC.

Clinical profile and response to adjuvant treatments in patients with follicular dendritic cell sarcoma in the United States: Insights from SEER analysis.

e23537 Background: Follicular Dendritic Cell Sarcoma (FDCS) is a rare, indolent, low-grade sarcoma known for local recurrences managed primarily by surgery. The role for adjuvant therapy has not been established for either radiation or chemotherapy. We aimed to comprehensively analyze clinical and epidemiological profiles and responses to treatment in these patients. Methods: This is a retrospective study using the National Cancer Institute (NCI) Surveillance, Epidemiology, and End Result (SEER) database. Cases of FDCS between 2001 to 2022 were identified utilizing the International Classification of Diseases for Oncology edition 3 (ICD-O-3) code 9758/3. Only adults &gt; 18 years of age and diagnosed by positive histology or cytology were included. Descriptive statistics were used to describe demographic and tumor characteristics. Logistic regression was used to identify the factors influencing survival. Kaplan-Meier method was used to plot survival based on different treatment regimens and stages. Results: A total of 168 patients with FDCS were identified, with more than 50% of the patients ≥ 50 years of age. The mean age at diagnosis was 52.6 years, 56% were female, and 74.4% were white. Most of the patients had localized disease (63.7%), 17.9% had distant disease, and the remaining had unknown stages. About 90% of the patients underwent surgery, with 41% receiving local tumor excision. In Univariate analysis, older age, and distant disease were found to have poor outcomes. Surgery, irrespective of stage, was found to improve overall Survival (Table 1). While chemotherapy and distant disease had poor outcomes in univariate analysis, they were not statistically significant in multivariate analysis. The majority of the patients who received chemotherapy alone without surgical intervention had distant disease, explaining the poor outcome seen in univariate analysis. Among 107 patients with localized disease, 41 patients (41.1%) underwent only surgery and 43 patients (40.1%) received adjuvant therapy (either chemotherapy or radiation vs both) along with surgery. 5-year overall survival was significantly lower in patients who received adjuvant therapy. (88.4% vs 68.4%, p = 0.001). Conclusions: In conclusion, FDCS has a fair overall 5-year survival with surgery alone. Patients with localized disease, who received adjuvant therapies had poor survival outcomes as compared to the surgery-only group owing to disease burden. Large prospective studies are required to properly evaluate the benefit of adding chemotherapy or radiotherapy in resectable disease.

Real-world (RW) antiemetic use and its association with duration of oral azacitidine (Oral-AZA) maintenance in patients (pts) with acute myeloid leukemia (AML) in the United States (US).

e23259 Background : Oral-AZA was approved in the US in Sep 2020 for maintenance treatment of transplant-ineligible pts with AML in remission following intensive chemotherapy. Approval was based on the QUAZAR trial (NCT01757535), which showed that Oral-AZA was associated with longer survival outcomes than placebo in this pt population. Both the prescribing information and clinical guidelines recommend antiemetic prophylaxis with Oral-AZA for at least the first 2 cycles to prevent the most common adverse events, nausea and vomiting. However, the extent to which antiemetics are being used with Oral-AZA in the real world is not yet well understood. This study aimed to examine the use of antiemetics among pts with AML receiving Oral-AZA in RW clinical practice and to determine whether this has any association with duration of therapy (DoT). Methods : This was a retrospective, observational study using Flatiron Health electronic health record data from Jan 2014 to Apr 2023. Eligible pts were ≥18 years and had a diagnosis of AML and ≥1 order for Oral-AZA on or after Sep 1, 2020. The index date was date of Oral-AZA initiation. Pts were followed until death, loss to follow-up, or the end of the study. Pt characteristics were assessed on the index date; antiemetic use was assessed at index and over the follow-up period. For each pt, each 28-day cycle of Oral-AZA was denoted as “covered” or “not covered” by antiemetics according to whether the pt had ≥14 days of antiemetics available during the cycle. Total DoT was measured for Oral-AZA using cumulative incidence curves and compared between pts with their first 2 cycles covered and those without. Results: 189 pts with AML were included. Mean age was 66 years, 52% were female, 56% had evidence of prior cytarabine use, and 10% had a prior stem cell transplant. 152 pts had ≥2 cycles of Oral-AZA. Overall, less than half of pts (48%) had a claim for an antiemetic on the index date. 16% never initiated an antiemetic between index and the end of follow-up; in the remaining 84%, the mean time from the index date to antiemetic initiation was 57 days and 29% had a time to antiemetic initiation of &gt; 56 days. Only 9% (14/152) of pts had both their first 2 Oral-AZA cycles covered by antiemetics. Overall, pts had a median of 5 Oral-AZA cycles. Pts with antiemetic coverage of their first 2 cycles had a median of 8.5 Oral-AZA cycles versus 6 in those without. The median DoT was longer for pts with antiemetic coverage of cycles 1 and 2 than those without (258 days vs 154 days). Conclusions: These findings suggest that antiemetics are not currently widely utilized with Oral-AZA in RW US clinical practice. This may reduce DoT and could potentially impact the likelihood of observing RW efficacy outcomes like those in the QUAZAR trial. Further studies are required to examine the association between guideline-recommended antiemetic use and clinical outcomes.

Prognostic factors for patients with sarcoma with brain metastases.

e23542 Background: Sarcomas arise in mesenchymal tissue occurring anywhere in the body with a propensity to metastasize often to the lung, liver, and bones. The brain is a rare site of metastasis with increasing incidences found in those relapsing after prolonged disease control with treatment. Brain metastases development has been associated with dismal prognoses, and more data is necessary to assess factors for improved outcomes of patients. Methods: The retrospective cohort includes 81 patients diagnosed with sarcomas metastasizing to the brain treated at five sarcoma centers between 1/1998 and 12/2021. Demographic data, characteristics and presentation of brain metastases, and treatment modalities for malignancy were identified and analyzed. Results: In total, there were 45 men and 36 women with the mean age of diagnosis being 43 years. Upon presentation, 89% of patients were symptomatic with the most common presenting symptom being focal neurological deficits (37.9%) and headaches (22.1%). At the time of analysis, 58 patients (71.6%) had died of metastatic sarcoma, 16 patients (19.8%) were alive with disease, and 3 patients (3.7%) were alive without evidence of disease. The most frequent histologies were leiomyosarcoma (12.3%) and undifferentiated pleomorphic sarcoma (12.3%). In 70.4% of patients, the tumor also had metastasized to the lung. Median time from sarcoma diagnosis to brain metastases was 1.9 years (range: 0-34.6 yrs). Median time from diagnosis of brain metastases until death was 6 months (range: 0.5-330 mo). Treatment modalities of brain metastasis varied widely with 18 patients (22.2%) undergoing whole brain radiation therapy (WBRT), 11 (13.6%) undergoing systemic chemotherapy and WBRT, and 10 (12.3%) undergoing combined surgery, systemic chemotherapy, and stereotactic radiosurgery. In multivariate analysis, the variables identified as statistically significant for predicting improved survival outcomes included surgery (HR 0.30) and chemotherapy (HR 0.24), but not radiation therapy. In patients undergoing surgery or chemotherapy, the median survival time after brain metastasis diagnosis was markedly improved, with 13.9 months and 12 months respectively versus the overall patient median of 6 months. In patients undergoing radiation therapy, there was significantly improved survival with stereotactic radiosurgery (SRS, mOS 11.6mo) as opposed to whole brain radiation therapy (WBRT, mOS 8.3mo) probably due to decreased mean number of brain metastases found in those necessitating SRS (3.2) compared to WBRT (5.7). Conclusions: Together, our findings identify that patients with metastatic sarcoma to the brain have poor prognoses, often have concurrent metastasis, and have median survival of only 6 months. However, there were significantly improved outcomes with interventions such as surgery, chemotherapy, or SRS, suggesting that aggressive treatments are warranted despite the overall poor prognosis.

Unveiling the cost-effectiveness of CDK4/6 inhibitors in treating patients with HR+/HER2- metastatic breast cancer: A closer look at nonmedication expenses.

1532 Background: Cyclin-dependent kinase (CDK)4/6 inhibitors have significantly enhanced survival outcomes in postmenopausal patients diagnosed with HR+ MBC. Their integration with endocrine therapy (ET) has become the standard of care in MBC treatment lines. There are limited economic evaluations of these innovative, yet costly, therapies. This study assesses the cost-effectiveness of these drugs using EHR derived data and administrative claims to estimate cost. Methods: We used the nationwide EHR-derived Flatiron Health (FH) de-identified database to identify 3,879 patients receiving 1st line (1L) treatment for HR+ MBC (2,137 received CDK4/6i+ET and 1,742 received ET alone) between Feb 2015 and Nov 2021. SEER-Medicare claims data was used to supplement the missing cost info in the FH database to quantify monthly medication costs, drawing data from Medicare patients continuously enrolled in PARTs A, B, and D between 2015 to 2021 for at least 24 months and specific to therapeutic approaches for MBC and overall healthcare costs. The costs were adjusted by the patient characteristic: age, race, specific ET or CDK4/6i drug, and Medicare dual eligibility. The effectiveness was measured as progression-free duration in months. All costs were adjusted for inflation. The Incremental Cost Effectiveness Ratio (ICER) analysis was conducted to examine the cost-effectiveness of CDK4/6i as compared with ET alone. Results: Average estimated monthly medication costs were $12,524 and $322 for CDK4/6i+ET and ET alone, respectively. On average, CDK4/6i+ET increased the estimated medication costs by $235,564 over the time to first progression and was associated with a gain of 3.2 months of progression-free survival as compared to ET alone, resulting in an ICER of $73,098 per month without progression. At a willingness-to-pay of $65,000 per month without progression, both groups have 50% probability of being considered cost-effective. Notably, the average estimated monthly non-medication costs (total costs-medication costs) for the CDK4/6i+ET group were $2,278 compared to $4,265 for the ET alone group (p&lt;0.001). On average, CDK4/6i+ET decreased the estimated non-medication costs by $ 22,427. For non-medication costs, the ICER drops to $7,178 per month without progression making the CDK4/6i+ET the dominant cost-effective choice over ET alone. Conclusions: Cost-effectiveness of treating HR+ MBC patients is primarily driven by the cost of CDK4/6i drug prices. However, findings highlight significantly lower overall non-medication healthcare costs using CDK4/6i+ET compared to ET alone in 1L treatment. These cost savings, however, are offset by the high medication costs of CDK4/6i. Thus, lowering the market cost of CDK4/6i drugs or targeting those who can benefit the most could shift the balance in favor of a cost-effective benefit from Medicare perspective.

Primary intracranial germ cell tumors in adolescents and adults: Results of an international, multicenter, retrospective cohort study.

2061 Background: Primary Intracranial Germ Cell Tumors (iGCT) are rare. Previous prospective and retrospective studies mainly included pediatric patients (pts) with a median age of 10-14 years. The aim of this retrospective analysis was to evaluate characteristics, treatment and outcome of adolescents and adults with iGCT. Methods: Data were collected from 10 institutions in Germany and Switzerland. Pts aged &gt;/= 16 years at first diagnosis or at relapse with a primary iGCT were included. Objective responses were evaluated by local investigators. Statistics (Cox proportional hazard model, progression-free survival (PFS) and overall survival (OS) analyzed by Kaplan-Meier method) were performed with SPSS v29. Results: We identified 75 pts (92.0% male) with a median age of 23 years (range 16-60, 94.7% &gt;/= 18 years). At first diagnosis, histology was pure germinoma in 70.7%, pure teratoma in 10.7%, other non-germinomatous GCT (NGGCT) in 13.3%, unknown in 5.3% of pts. Localized, bifocal, and metastatic disease was found in 72.0, 6.7, and 21.3% of pts. As part of their first line (1L) treatment, 69.3%, 80.0%, and 62.7% received surgery, radiotherapy, and chemotherapy, respectively. High dose chemotherapy/ autologous stem cell transplantation (HDCT/ASCT) was part of 1L treatment in n=3 pts with NGGCT. Trimodal and bimodal treatment was performed in 48.0% and 32.0% of pts. Response to 1L therapy was complete remission (CR) in 61.3%, partial remission tumor marker negative (PRm-) in 16.0%, PRm+ in 4.0%, PR with tumor marker status unknown in 4.0%, progressive disease (PD) in 2.7%, and unknown in 12.0%. Relapse occurred in 13/75 pts (17.3%) with unknown histology (n=4), teratoma (n=2), other NGGCT (n=4), and germinoma (n=3). In 2 pts. in whom germinoma was diagnosed at time of first diagnosis, at time of recurrence PNET and Yolk sac tumor were histologically proven. Median time to relapse was 19.0 months (mo.; range 3-223). HDCT/ASCT as salvage treatment was performed in 5 pts with NGGCT and in one pt with germinoma as 2L (n=5) or 3L (n=1). NGGCT histology was associated with increased risk for recurrence or death (p=0.012 and 0.039).3-year PFS was 90.7% (germinoma: 98.1%, NGGCT: 73.9%) and 5-year OS was 92.0% (germinoma: 98.1%; NGGCT: 78.3%). Median follow-up time was 60 mo (range 0-339). Conclusions: Disease characteristics, treatment and outcomes of adolescent/ adult iGCT pts are comparable to those reported in pediatric pts. High cure rates are achieved in pts with pure germinoma and current treatment concepts. In pts with NGGCT further investigation is needed to improve survival outcomes.

Survival outcome prediction of breast carcinomas on whole-slide histopathology images using deep learning.

1070 Background: Breast cancer is the most common cancer among women with 2 million new cases and 627,000 deaths in 2020. Early diagnosis and effective treatment are crucial for improved outcomes. Prognosis mainly depends on histopathological features, among them grade. As whole slide histopathology image (WSI) of tumor tissue contains a huge amount of hidden morphological features unexploited by pathologists, we investigate the potential of Artificial Intelligence (AI)-based analysis on WSI to predict prognosis in terms of 5-year overall survival in breast cancer patients. Methods: We used a novel deep neural network (DNN), DiaDeepBreastPRS, designed specifically for predicting a survival risk score in breast cancer patients based on H&amp;E-stained whole slide images (WSI) of tumor tissues. The model incorporates two distinct viewpoints, one capturing cellular details and the other the tissue-level information. DiaDeepBreastPRS was trained and evaluated on a multi-centric discovery cohort of 1,027 patients (1,095 H&amp;E WSI) from the TCGA-BRCA dataset using a cross-testing and cross-validation technique. It was evaluated on an external cohort, comprising 232 patients (247 H&amp;E WSI). A statistical analysis with a multivariate Cox regression model was carried out on clinico-pathological data. AI scores and the concordance index (c-index) serves as the metric for assessing the performance. The predicted risk scores were used for effective risk stratification of breast carcinomas. Results: On the TCGA-BRCA dataset, the model achieved an average c-index of 67%, which reaches 78% by adding the pTNM stage and age at diagnosis. On the external dataset, the model achieved a c-index of 66% and 75% when including some histopathological prognosis factors (pTNM stage, age at diagnosis, HER2 and HR status and mitosis). The AI score was independently associated with the survival of breast cancer patients with the highest hazard ratio (HR 2.46, p&lt;0.005). Furthermore, the model was able to significantly discriminate between the 2 groups of patients, with a good and a poor prognosis in terms of overall survival (p&lt;0.005). Conclusions: In this study, we showcased that the algorithm was able to instantly extract prognostic morphological features from H&amp;E whole slide images (WSI) and could be included in the pathology report. This could potentially enhance clinical decision-making, elevating the standard of care. Compared to commonly used molecular signatures, the AI algorithm enables a reduction in response time and cost savings. However, further investigations using additional independent cohorts are essential to consolidate the algorithm's performance and allow its generalizability, establish its superiority over existing prognostic markers, and provide insights into its interpretability.

Correlating survival outcomes in patients with advanced prostate cancer with novel hyperpolarized 13C MRI metabolic imaging biomarkers.

e15059 Background: Hyperpolarized 13C (HP 13C) MRI is a novel molecular imaging approach that detects aberrant aerobic metabolism, namely elevated rates of pyruvate-to-lactate conversion (kPL), in patients with advanced malignancies. Higher kPL has been shown to correlate with higher tumor grade among patients with localized prostate cancer (PC). This research sought to evaluate the correlation between kPL and clinical outcome measures in patients with advanced PC. Methods: Patients with metastatic or locally advanced PC (castration sensitive or resistant) were prospectively enrolled at our institution and underwent HP 13C MRI of one or more target lesions identified on prior conventional imaging. Voxelwise kPL values were computed in MATLAB using an inputless two site exchange model. kPL,median was defined as the median kPL value per-patient across all target lesions; kPL,kurtosis measured the tailedness of the kPL distribution per-patient. We retrospectively analyzed progression free survival (PFS) and overall survival (OS) in subgroups divided by metabolic activity below versus above cut-point (kPL,median &lt;0.017 s-1 and ≥ 0.017s-1, respectively). Survival statistics were calculated using the Cox PH model. Results: Sixteen patients (6 with castration-sensitive and 10 with castration-resistant PC) were accrued. With a median follow-up of 22.0 months from the date of MRI, the lower-kPL subgroup had significantly longer median PFS (11.2 vs 0.5 months; p&lt;0.01) and OS (NR vs 18.4 months; p&lt;0.05) compared to the higher-kPL subgroup. By comparison, baseline serum PSA (PFS: p=0.19, OS: p=0.41) and LDH (PFS: p=0.60, OS: p=0.34) did not demonstrate a significant association with clinical outcomes. There was a strong negative correlation between kPL,kurtosis and OS (r = -0.75), and moderate negative correlations between kPL,median and OS (r = -0.45) as well as kPL,max with both PFS (r = -0.48) and OS (r = -0.54). There was no significant kPL,median difference between castration-sensitive and resistant subgroups (0.015±0.011 vs 0.016±0.006 s-1, p&gt;0.8). Conclusions: HP 13C MRI-derived non-invasive metabolic biomarker kPL,median significantly correlated with clinical outcome measures in a retrospective analysis of patients with advanced PC, outperforming established serological prognostic markers PSA and LDH. Limitations include our small sample size, retrospective design, and heterogeneous patient population. Nevertheless, these encouraging preliminary results support further investigation of HP 13C MRI as a prognostic and/or predictive PC biomarker in multi-center prospective imaging trials. [Table: see text]

Galectin-3-Binding Protein Inhibits Extracellular Heparan 6-O-Endosulfatase Sulf-2

Human extracellular 6-O-endosulfatases Sulf-1 and Sulf-2 are the only enzymes that post-synthetically alter the 6-O sulfation of heparan sulfate proteoglycans (HSPG), which regulates interactions of HSPG with many proteins. Oncogenicity of Sulf-2 in different cancers has been documented, and we have shown that Sulf-2 is associated with poor survival outcomes in head and neck squamous cell carcinoma (HNSCC). Despite its importance, limited information is available on direct protein–protein interactions of the Sulf-2 protein in the tumor microenvironment. In this study, we used monoclonal antibody (mAb) affinity purification and mass spectrometry to identify galectin-3-binding protein (LG3BP) as a highly specific binding partner of Sulf-2 in the conditioned media of HNSCC cell lines. We validated their direct interaction in vitro using recombinant proteins and have shown that the chondroitin sulfate (CS) covalently bound to the Sulf-2 influences the binding to LG3BP. We confirmed the importance of the CS chain for the interaction by generating a mutant Sulf-2 protein that lacks the CS. Importantly, we have shown that the LG3BP inhibits Sulf-2 activity in vitro in a concentration-dependent manner. As a consequence, the addition of LG3BP to a spheroid cell culture inhibited the invasion of the HNSCC cells into Matrigel. Thus, Sulf-2 interaction with LG3BP may regulate the physiological activity of the Sulf-2 enzyme as well as its activity in the tumor microenvironment.

Impact of boarding time on in-hospital mortality in patients with cancer presenting to the emergency department.

11036 Background: Longer emergency department (ED) boarding times for admitted patients is associated with increased morbidity and mortality.1 While research over the years has shown an association between boarding time to mortality in a variety of patient demographics, no specific research has been explored in a cancer population. Patients with cancer visit the emergency department frequently and have a high rate of admission compared to other patients.2 This study evaluates boarding times and mortality rates in patients presenting to an oncologic ED. Methods: A retrospective analysis was performed on 183,524 ED visits located at a comprehensive cancer center between March 2016 and December 2022. Eligibility criteria included patients 19 years and older admitted to the hospital excluding direct intensive care unit admission. Boarding time was defined from the time the physician made an order to admit to the hospital to the time of ED departure. Demographics and clinical characteristics were examined using descriptive statistics. Categorical data was analyzed using chi-square test and continuous variables employed the nonparametric Mann–Whitney U test. Boarding time was grouped into quartiles. Univariate and multivariable logistic regression analyses examined clinical factors, including boarding time and in-hospital mortality. Results: The eligible number of visits supporting the study equaled 83,629. Overall median boarding time was 2.7 hours (interquartile range: 1.5–5.1 hours) and in-hospital mortality was 5.5% (n=4607). Longer boarding time was significantly associated with in-hospital mortality. Patients with boarding time ≥5.1 hours had 1.19 (95% confidence interval [95%CI]: 1.09-1.30; P&lt;0.001) odds of in-hospital mortality when compared to the reference group (boarding time &lt;1.5 hours) when controlling for other risk factors including comorbidities and emergency severity index (ESI) between 1 through 5. Similar results were observed for patients with boarding times of ≥1.5- &lt;2.7 hours and ≥2.7- &lt;5.1 hours with odds ratio of 1.12 (95%CI: 1.02-1.22; P=0.013) and 1.11 (95%CI: 1.02-1.21; P=0.020), respectively. Higher Charlson comorbidity index and levels 1 and 2 ESI were also associated with poor survival outcome (P&lt;0.001 for both). Conclusions: This study found an association between boarding time and in-hospital mortality in cancer patients presenting to the ED. Patients with longer boarding times were likely to experience mortality during their hospital admission. High comorbidity score and high-risk ESI were also identified as risk factors for poor survival outcome. These results emphasize the need for improved strategies to expedite the admission process and optimize care for cancer patients in the ED to reduce mortality rates. Further research and interventions targeting reduction in boarding times are warranted to improve outcomes for this vulnerable population.

Colorectal Cancer Survival and Its Prognostic Factors in Karachi, Pakistan.

To determine the survival rates of colorectal cancer (CRC) in the Pakistani population and determine the prognostic factors for survival among the CRC patients. Retrospective cohort study. Place and Duration of the Study: The cancer registry of the Aga Khan University Hospital, Karachi, Pakistan, from 2010 to 2016. The abstracted data from the cancer registry was cleaned and updated regarding the vital status at the last follow-up. Survival analyses were performed using the Kaplan-Meier method. Adjusted hazard ratios (aHR) and their 95% confidence intervals (CIs) were estimated using a cox regression model to assess the prognostic factors for survival. The overall proportion of late-onset CRC (>50 years of age) was 55.3% and early-onset CRC (<=50 years of age) was higher than expected (45.7%). A high level of carcinoembryonic antigen (CEA) (>5 ng/ml) was associated with poor survival compared to patients with CEA levels of ≤5 ng/ml (aHR = 1.68, 95% CI = 1.04, 2.72). Patients, who experienced recurrence, showed poorer survival (aHR = 4.27, 95% CI = 2.55, 7.14). Patients, who did not undergo surgery, showed significantly poorer survival compared to those who underwent surgery (aHR = 5.53, 95% CI = 2.35, 13.03). The findings suggest that monitoring CEA levels, ensuring prompt surgical treatment and follow-up care for recurrent cases can improve survival outcomes in patients with colorectal cancer. Colorectal cancer (CRC), Surgery, Recurrence, Grade, Cancer registry.