Citations

9002 Background: The field of AI is rapidly evolving. With recent development of more user-friendly AI software, its integration into healthcare across different medical specialties, including HemOnc has emerged. Data detailing the perception and concerns of the HemOnc workforce about AI’s roles is lacking and is needed if AI is to be integrated in HemOnc CliPr and MedEd. Methods: Questionnaires about the perception and concerns regarding AI in CliPr and MedEd were created on REDCap and approved by IRB. We surveyed the entire HemOnc workforce at the 3 Mayo Clinic major sites between 11/07/24 and 01/20/25, including physicians, both faculty (FAC) and fellows (FEL), advanced practice providers (APP), and nurses (RN). Participation was voluntary. Simple statistical analyses were employed for the results. Results: 344 participants (PTP) responded to the survey, 118 physicians (41 FEL and 77 FAC), 49 APP, and 177 RN. 64% of PTP report having used AI but only 31% used it in HemOnc MedEd, and 28% in HemOnc CliPr, with 67% considering themselves to have little to no knowledge about AI. 94% of PTP believe AI will be integrated in HemOnc MedEd, with such integration being seen as beneficial by 90%. Among physicians, 85% of FEL and 92% of FAC report that fellowship programs should incorporate AI training into curricula. 95% of PTP believe AI will be incorporated into HemOnc CliPr. Meanwhile, 62% of PTP (50.8% of physicians, and 68% of APP and RN) are concerned about risks it may pose to CliPr. Nevertheless, 90% of PTP would embrace AI’s use in HemOnc. Table 1 details the perceptions and concerns about AI in HemOnc MedEd and CliPr. The main perceived risks are decreased time spent with patients (pts), and inaccuracies or worse pt care. Meanwhile, 33% believe AI would increase efficiency and quality of care, while 30% believe it would increase time spent with pts. 14% of PTP worry their role could be replaced by AI. Conclusions: To the best of our knowledge, this is the largest assessment of HemOnc workforce’s perception and concerns about AI. Based on our survey, the HemOnc workforce, in general, endorses AI use, but with some concerns raised. While incorporation in MedEd is perceived with excitement, many envision the use in CliPr involves risks and challenges. Proper systematic education of the workforce about AI, with well-designed CliPr integration methods are needed to mitigate the legitimate existing concerns. Perceptions & concerns about AI in HemOnc MedEd & CliPr. FEL % APP % RN % FAC % AI will assist documentation in CliPr 98 82 79 92 AI will be used in pt communication 73 80 78 87 AI will screen pts for clinical trial enrollment 85 86 76 96 AI will increase the efficiency and quality of CliPr 43 37 24 46 AI will increase time spent with pts 39 27 25 38 AI will decrease time spent with pts 29 41 48 23 AI will lead to inaccuracies or worse CliPr 12 20 25 20 AI may replace the HemOnc workforce 11 16 19 5

e16481 Background: Gastric cancer is a malignant disease characterized by the uncontrolled growth of cells in the stomach lining. It is a global health concern with regional variation in incidence and prevalence. This study investigates the regional incidence and prevalence of gastric cancer among adults aged 70 and older from 1990 to 2021, utilizing data from 26 global regions. Methods: Global Burden of Disease (GBD) data for 2021 were analyzed to assess regional incidence and prevalence of gastric cancer among adults aged ≥ 70. The Annual Average Percentage Change (AAPC) was calculated to evaluate trends from 1990 to 2021, with statistical significance determined using p-values. Results: In 2021, East Asia has the highest incidence (273403) followed by Middle SDI (189383) and High-middle SDI (176691). Highest Prevalence numbers were recorded for East Asia (398,000) followed by High SDI (337,000) and High-middle SDI (250,000). With regards to rates per 100,000, Oceania has the lowest incidence (257) as well as prevalence (252) followed by Central Sub-Saharan Africa (I:1142 , P: 1081) and Southern Sub-Saharan Africa (I:1295, P: 1227). The largest increase in AAPC of incidence was exhibited by Western Sub Saharan Africa (-0.24, CI: -0.27 to -0.23), Southern Sub Saharan Africa (-0.29, CI: 0.37 to -0.22), and South Asia (-0.306, CI: -0.422 to -0.158) regions, while South Asia (-0.087, CI: -0.1748 to 0.0308), East Asia (-0.0952, CI: 0.0284 to 0.1606), and Andean Latin America (-0.1696, CI: -0.3498 to -0.0381) showed largest increase in AAPC of prevalence. Western Europe region had the greatest decline in AAPC of incidence (-2.3995, CI: -2.4374 to -2.3691) followed by Central Europe (-2.2010, CI: -2.3007 to -2.1445) and Eastern Europe (-2.1554, CI: -2.212 to -2.0925 ) regions while Central Asia had the greatest decline in AAPC of prevalence (-1.9281, CI: -2.0109 to -1.8522) followed by High Income Asia Pacific (-1.8268, CI: -1.8926 to -1.7913) and Eastern Europe (-1.8103, CI: -1.8631 to -1.7623). All AAPC values were statistically significant (p < 0.000001). Conclusions: The East Asia region exhibited the highest incidence and prevalence, highlighting the vulnerability of these populations, while Central Sub-Saharan Africa bore the least burden. Notably, several regions, particularly in Asia, experienced substantial increases in both incidence and prevalence, emphasizing the need for targeted interventions. Conversely, some regions, such as Europe, showed encouraging declines in prevalence, suggesting that effective prevention and control strategies can be implemented. These findings underscore the importance of tailored approaches to address the evolving burden of Gastric Cancer.

e16479 Background: Recent genomic data has demonstrated SBA to be a molecularly unique entity when compared to colon or gastric cancers. The ongoing SWOG 1922 randomized clinical trial is comparing FOLFIRI to ramucirumab/paclitaxel as the second-line treatment for metastatic SBA. We sought to further define the activity of taxane-based therapy in the largest collection of SBA patients treated with this therapy. Methods: A retrospective review of SBA patients treated with taxane-based chemotherapy from 1994 to 2024 at MD Anderson Cancer Center was performed. All patients had pathologic confirmation, received > 1 cycle of therapy, and had documented tumor response evaluation. Response was assessed by the treating physician based on the imaging studies and categorized as response, stable disease or progression. Patient demographics, clinical parameters, molecular data, and taxane treatment was reviewed. Kaplan-Meier survival analysis was performed to calculate time to progression (TTP) and overall survival (OS). Results: 70 SBA patients treated with taxane-based therapy were identified. The median age at diagnosis was 57 years (range 33-80 years), majority being male (59%) with primary tumor located at duodenum (44%), Jejunum (34%), Ileum (16%). The most common presenting metastatic site was peritoneum (39%), followed by liver (31%). The genomic status revealed mutations in the following genes: 62% TP53, 47% KRAS, 24% SMAD4, and 15% APC. Taxane treatment was single agent (nab-paclitaxel, paclitaxel, or docetaxel) in 29%, gemcitabine and taxane combination in 61% and other taxane-based combinations in 10%. Therapy was given in the metastatic setting as 2nd-line in 40%, 3rd-line in 33% and 4th-line or greater in 20%. Response status was response in 24%, stable disease in 26%, and progression in 50%. Median TTP was 3.1 months (95%CI: 2.0-4.2 months), and median OS was 8.7 months (95%CI: 7.4-10.1 months). Median TTP was similar between single agent (2.6 months) and gemcitabine-based combination (2.5 months) (p =0.75). Efficacy did not differ by line of therapy nor primary tumor site. Efficacy differed by TP53 mutation status: TP53 mutated vs wildtype (response 21% vs 43%, p = 0.02; median TTP 2.4m vs 4.9m, p = 0.013; median OS 7.3m vs 10.6m, p = 0.004). Conclusions: This retrospective study of 70 SBA patients confirms the activity of taxane-based therapy demonstrating a response rate of 24% and median TTP of 3.1 months. Though limited by sample size, TP53 mutations may represent a negative predictive marker for taxane-based therapy in SBA patients. These findings support the ongoing SWOG 1922 trial investigating taxane-based therapy as a second line for metastatic SBA.

12005 Background: Young adults (YAs) diagnosed with cancer between the ages of 18 and 39 face unique psychosocial challenges and are at risk of experiencing significant emotional distress and poor health-related quality of life (HRQOL). This randomized trial evaluated the efficacy of Bright IDEAS-YA, a problem-solving skills training intervention, on reducing distress and improving HRQOL of YAs newly diagnosed with cancer. A secondary aim examined change in problem-solving ability as a potential mediator of treatment effects. Methods: A three-site randomized trial of Bright IDEAS-YA compared with enhanced usual care (EUC) enrolled YA survivors within four months of a first diagnosis of cancer. Participants were randomized 1:1 to Bright IDEAS-YA or EUC (NCT04585269). Bright IDEAS-YA is a 6-session, one-on-one intervention that teaches a systematic approach to overcome personal challenges across any life domain. EUC involved usual psychosocial care plus AYA resources. Participants completed surveys at 0 (baseline), 3, 6, 12, and 24 months, with 6 months as the primary endpoint. Validated measures included the PROMIS Depression Short Form and Anxiety Short Form (primary outcomes), the Functional Assessment of Cancer Therapy – General (FACT-G; primary outcome), and Social Problem-Solving Inventory-Revised Short Form (SPSI-R; mediator). Efficacy was tested using linear mixed effects models, run in R, examining the group x time interaction effects. Mediation was tested using the R multiple mediation analysis. Results: 344 YA (34.2% acceptance rate, M age = 30.3 years, SD = 6.3; 63% female, 37% male, < 1% non-binary) participated (100% planned enrollment), with 86% and 81% completing surveys at 3 and 6 months, respectively. Compared to baseline, the intervention arm showed statistically significant improvements in depression, anxiety, and HRQOL relative to the control group at 6 months. The intervention arm demonstrated an average reduction of 3.2 T-score points reduction in depression (95% CI [-4.9, -1.5], p < 0.001), 2.4 T-score points in anxiety (95% CI [-4.0, -0.81], p = 0.003), and 3.4 points improvement in total FACT-G (95% CI [0.34, 6.5], p = 0.029) relative to the control. These differences reflect clinically meaningful changes per published reports. Across all three models, change in total problem-solving ability (SPSI-R) was shown to mediate treatment effects, primarily due to change in the negative problem-orientation subscale. Conclusions: Bright IDEAS-YA was efficacious in reducing symptoms of depression and anxiety and improving HRQOL compared with enhanced usual care among YAs with cancer. Improvements are attributable to increased problem-solving ability, particularly by reducing the tendency to view problems as significant threats and doubt one’s ability to successfully solve problems. Clinical trial information: NCT04585269 .

4123 Background: Atezolizumab plus bevacizumab is the most commonly utilized first-line therapy for advanced HCC. However, the optimal choice for second-line treatment remains uncertain, particularly between different tyrosine kinase inhibitors including lenvatinib and cabozantinib. This study aims to compare survival outcomes of patients with metastatic HCC who received either lenvatinib or cabozantinib as second-line therapy following frontline treatment with atezolizumab plus bevacizumab. Methods: This retrospective cohort study utilized the TriNetX database, a large-scale platform providing access to deidentified electronic medical records from over 130 million patients across 94 healthcare organizations in the United States. The study included patients diagnosed with metastatic HCC (ICD-10 codes: C22, C22.8) who were aged 18 years or older, diagnosed between January 2019 and October 2024, and had received first-line chemotherapy with atezolizumab and bevacizumab. The cohort was divided into two groups: one receiving lenvatinib and the other cabozantinib as second-line therapy. The primary outcome was overall survival (OS), compared between the two treatment groups using 1:1 propensity score matching (PSM) to balance baseline demographics and comorbidities. Kaplan-Meier survival analysis, log-rank tests, and hazard ratios (HR) were employed to assess differences in OS. Results: Between January 2019 and October 2024, a total of 552 patients met the study criteria, including 397 patients who received Lenvatinib and 155 patients who received cabozantinib as second-line therapy. Median age was similar in two groups (65.2 vs 65.9 yrs). There were no differences between the two groups with respect to gender, albumin or bilirubin levels. Lenvatinib group had lower proportions of white patients (44.1% vs 55.3%). After PSM (matched on age, race, gender, albumin and bilirubin), the final analysis included 151 patients in each treatment group. Kaplan-Meier survival curves demonstrated no statistically significant difference in OS between the two groups (median OS: 16.6 vs 10.9 months; HR: 0.809; 95%CI: 0.576-1.136; p=0.597). Conclusions: This retrospective cohort study found no significant difference in OS in pts with metastatic HCC treated with lenvatinib or cabozantinib as second-line therapy following atezolizumab plus bevacizumab. These findings suggest that both agents may offer comparable survival benefits, highlighting the need for further prospective studies to refine second-line treatment strategies for advanced HCC.

4119 Background: TP53 mutations are frequent genetic alterations in cancers and also prevalent in biliary tract cancer (BTC). In non-small cell lung cancer, TP53 mutations have been reported to enhance immune checkpoint inhibitor (ICI) efficacy and improve outcomes. However, their impact on BTC remains unclear. This study investigated the clinico-molecular characteristics, prognosis, and ICI efficacy in TP53 -mutated BTC. Methods: Patient data were collected from the SCRUM-Japan GOZILA and MONSTAR-SCREEN-1/2 databases (Japan) and the Duke university and Mayo clinic databases (U.S.), which included patients receiving first-line ICI therapy. Comparisons between TP53 wild-type (WT) and mutation groups were performed in the Japanese cohort. Subsequently, analyses were expanded to include U.S. patients, focusing on comparisons between non-ICI and ICI groups. Tumor Immune Dysfunction and Exclusion (TIDE) scores were calculated using MONSTAR-SCREEN-2 whole transcriptome sequencing (WTS) data to evaluate ICI responsiveness, and gene set enrichment analysis (GSEA) explored pathways associated with TP53 mutations. Results: In the Japanese cohort (n=594), TP53 mutations were identified in 311 patients (52.4%). KRAS , ERBB2 , CDKN2A , and SMAD4 alterations were more frequent in the TP53 mutation group, while IDH1, BAP1 , and FGFR2 fusions were more common in the WT group. Multivariable analysis showed TP53 mutations were independent prognostic factors for poor outcomes (progression-free survival [PFS]: HR 1.37, 95% CI: 1.11–1.69, P=0.003; overall survival [OS]: HR 1.36, 95% CI: 1.06–1.75, P=0.017). Incorporating the U.S. cohort (n=625; non-ICI: 548; ICI: 77), no significant differences in overall response rate (ORR) or disease control rate (DCR) were observed in the non-ICI group between the groups. However, in the ICI group, TP53 mutations tended to show higher ORR (21.1% vs. 38.5%, P=0.16) and DCR (47.4% vs. 66.7%, P=0.14). In the non-ICI group, TP53 mutations were associated with worse PFS (HR 1.46, median PFS: 7.4 vs. 5.3 months, P<0.001), whereas, in the ICI group, no significant difference was observed; however, a trend toward better PFS was seen in the TP53 mutation group (median PFS: 5.0 vs. 6.4 months, P=0.163). TIDE scores were significantly lower in the TP53 mutation group, indicating higher ICI responsiveness. GSEA revealed enrichment of oxidative phosphorylation and hypoxia pathways. Conclusions: TP53 mutations are independent prognostic factors for poor outcomes in BTC. However, patients with TP53 mutations may derive greater benefits from ICIs, underscoring the importance of tailored therapeutic strategies in TP53- mutated BTC.

12011 Background: Patients (pts) with high HCT-Comorbidity Index scores (HCT-CI of ≥3), older age (≥65 years), and/or who are frail per gait speed (<0.8 meters/second) have increased morbidity and mortality after allo-HCT compared to younger and healthier counterparts. We report the phase II analysis (PIIA) and interim phase III primary outcome analysis (PIIIA) of a seamless phase II/III prospective, randomized clinical trial conducted at 11 transplant centers to test new approaches to improve quality of life (QOL) in this population. Methods: Phase II compared specialist-administered supportive and palliative care (SPC), patient-administered management of comorbidities (MC, e.g. physical exercise, stress reduction, etc), both (SPC+MC), and usual care (UC) for change in Functional Assessment of Cancer Therapy – Bone Marrow Transplantation (FACT-BMT) QOL scores from baseline to day 90 (D90). Pts deceased prior to D90 were assigned FACT-BMT score=0. The winning phase II arm moved forward versus UC in phase III. Results: PIIA was done after enrolling 35 pts to each of the 4 study arms. Calculating the difference between FACT-BMT scores on D90 minus baseline, excluding missing data, indicated that only SPC resulted in a small improvement in QOL compared to either MC or SPC+MC (Table); hence SPC was the winning phase II arm. The PIIIA was conducted after enrolling 158 SPC pts and 153 UC pts. The SPC and UC arms were well balanced with median age (both 68 years), HCT-CI ≥3 (49% vs 55%), frailty per gait speed (13% vs 12%), female sex (41% vs 34%), non-white race (9.5% vs 11.5%), and Hispanic or unreported ethnicity (7.7% vs 5.7%), respectively. After median follow-up of 362 days, 45 pts had died in each arm. The mean QOL difference between D90 and baseline was 2.83 for SPC and 4.27 for UC (difference of differences, -1.44, 95% CI of difference, -5.03 to 2.14, p=0.43). Fitting a generalized linear model that included baseline, D30, and D90 values and testing the null hypothesis that the slope of scores differs between SPC and UC resulted in p=0.85. Using the Kaplan Meier method, no difference in survival was observed across arms (HR 1.13 [0.75-1.73]). Conclusions: Specialist-administered palliative care showed no meaningful improvement in QOL, nor a survival advantage, compared to usual care in frail, older and comorbid allo-HCT recipients, resulting in the cessation of this Phase II/III trial. Analysis of the whole patient population for primary and secondary outcomes is in progress. Clinical trial information: NCT03870750 . Change in FACT-BMT (D90 value minus baseline value) comparing the 4 arms of phase II. Group Mean difference (sd) Median difference (range) SPC (n=28) -2.93 (28.52) 0.25 (-102 to 38.22) CM (n=18) -18.37 (33.80) -9.50 (-98.33 to 11) SPC+CM (n=27) -15.76 (32.69) -7.67 (-90 to 32)

12083 Background: Fatigue and sleep disturbance are prevalent during and after cancer treatment; sleep-related symptoms affect 30-50% of patients with cancer, and sleep-wake disruptions persist beyond the immediate post-surgical period in breast cancer (BC) survivors. Identifying demographic- and treatment-related factors associated with sleep-related symptoms during survivorship is critical to inform interventions for those at highest risk of sleep disturbance. Methods: Patients who were seen at least once at Mayo Clinic Rochester following an initial diagnosis of BC at age 18 or older and provided informed consent were prospectively enrolled in the Mayo Clinic Breast Disease Registry. Surveys mailed to this cohort included two 11-point numeric rating scale questions regarding difficulty falling asleep and staying asleep in the past week, with values for each ranging from 0 (no problem) to 10 (as severe as you can imagine). Participants who provided sleep-related information on the Year 1 survey (answered approximately one year after cancer diagnosis) were included. Participants were excluded if they had clinical or pathologic metastatic disease and/or recurrence prior to the Year 1 survey. Associations of sleep-related symptoms with demographic and clinical characteristics were assessed using multivariate linear regression models, fitting the sleep difficulty rating scale as the outcome and clinical and demographic factors as exposures. Results: In total, 3,354 participants met inclusion criteria. The average age at BC diagnosis was 59, and most participants were female (99.3%), White (95.4%), non-Hispanic (96.2%), married (78.1%), had at least some college education (80.4%), did not report financial insecurity (76.2%), did not consume alcohol (60.6%) or smoke tobacco (93.2%), and reported at least some weekly exercise (76,6%). Sixty-two percent of participants had clinical stage 0 or I disease; 50.3% underwent lumpectomy (not mastectomy), 59.2% received radiotherapy, 34.1% received chemotherapy, and 67.2% received endocrine therapy. Overall, sleep-related symptoms were relatively low (mean rating for falling asleep = 2.1, mean rating for staying asleep = 3.1). In multivariate analyses, more difficulty falling asleep was associated with higher clinical stage (p < 0.001), more cigarettes smoked per day (p = 0.012), less moderate and/or strenuous exercise (p = 0.001), and more financial hardship (p < 0.001). More difficulty staying asleep was associated with higher clinical stage (0.003), older age (p < 0.001), more education (p = 0.011), and more financial hardship (p < 0.001). Conclusions: In our cohort of BC survivors, factors associated with both increased difficulty with falling and staying asleep at one year after diagnosis are higher clinical stage and more financial hardship. Future research should explore the course of these symptoms over time and across varied treatment trajectories.

12038 Background: CIPN, primarily associated with sensory neuropathy rather than motor or autonomic dysfunction, is a potentially long-term complication of cancer treatment including taxanes and platinums (T/Ps), and can negatively impact quality of life for breast cancer (BC) survivors. This project aims to quantify the severity of neuropathic symptoms at one and three years after diagnosis in BC survivors, comparing recipients of T/P to non-recipients. Methods: In the Mayo Clinic Breast Registry (MCBDR), a longitudinal cohort, surveys and medical record data from patients with stage 1-3 BC were used to understand the burden of neuropathic symptoms at 1- and 3-years post-diagnosis (denoted as Y1 and Y3). Y1 and Y3 raw scores from The Quality of Life Questionnaire-Chemotherapy-Induced Peripheral Neuropathy 20 (CIPN20) composite (CIPN20-C) and sensory subscale (CIPN-S) were converted to a 0-100 point scale, with lower scores corresponding to worse symptoms. Patients with BC recurrence prior to Y3 or incomplete surveys were excluded. We used two sample t-tests and multivariable linear regression modeling to compare recipients of T/P to non-recipients of T/P (with threshold for statistical significance p <0.05). Results: 786 patients were included, 112 of whom (14.2%) received T/P. T/P recipients were younger (p<0.001), more likely to have Stage II/III disease (p<0.001), and less likely to have received endocrine therapy (p<0.001). Univariate analyses revealed worse CIPN20-C score at Y1 (p=0.02) and worse CIPN20-S scores (p=0.004) at Y1 and Y3 in T/P recipients compared to non-recipients (Table). However, differences between the groups were no longer statistically significant after adjustment for age, stage and endocrine therapy. Conclusions: In this cohort, neuropathic symptom severity at Y1 and Y3 after a breast cancer diagnosis did not differ between recipients of taxane and/or platinum agents and nonrecipients after adjustment for age, stage, and endocrine therapy. These data may reassure patients and clinicians who are concerned about CIPN and considering use of these chemotherapies in this setting. Patient demographics and CIPN20 results. Clinical characteristic T/P recipients Non-recipients of T/P Age at diagnosis, mean (SD) 55.3 (11.6)* 59.8 (11.9) White race, N (%) 108 (96.4%) 660 (97.9%) Clinical stage II/III, N (%) 76 (68.5%)* 250 (37.5%) Endocrine therapy, N (%) 73 (65.2%)* 636 (94.4%) Diabetes mellitus, N (%) 9 (8.9%) 52 (8.6%) Y1 CIPN20-C score, mean (SD) 89.6 (10.9)* 92.0 (9.7) Y3 CIPN-C score, mean (SD) 89.4 (11.4) 91.1 (9.7) Y1 CIPN20- S score, mean (SD) 87.3 (15.1)* 91.3 (13.0) Y3 CIPN20-S score, mean (SD) 88.2 (14.1)* 91.1 (11.7) *Statistically significant (p <0.05) on univariate analysis.

TPS8113 Background: There are currently three approved approaches for patients with resectable NSCLC including neoadjuvant chemoimmunotherapy, adjuvant chemoimmunotherapy and perioperative treatment with neoadjuvant chemoimmunotherapy followed by adjuvant immunotherapy. All regimens were approved after showing event-free survival (EFS) or disease-free survival (DFS) benefit with the addition of immunotherapy to chemotherapy compared to chemotherapy alone. Each approach has its benefits and risks. Starting immunotherapy prior to surgery may improve treatment compliance and efficacy of immunotherapy. Nevertheless, neoadjuvant chemoimmunotherapy may result in missing an opportunity for curative surgery and increase the complexity of tumor resection. PROSPECT-LUNG (NCT06632327) is a randomized study evaluating whether starting chemoimmunotherapy before or after surgery leads to better outcomes. Methods: This is a randomized phase 3 trial in which patients will be randomized 1:1 to surgery followed by chemoimmunotherapy (adjuvant arm) or neoadjuvant chemoimmunotherapy followed by surgery and adjuvant therapy (perioperative arm). Patients with histologic or cytologic confirmation of surgically resectable stage IIA-IIIB NSCLC (per AJCC 9th edition) or stage IIA to IIIB per AJCC 8 th edition up to single ipsilateral mediastinal station (N2a), ECOG PS ≤ 2 (or Karnofsky ≥ 60%), no prior treatment for NSCLC and no previous malignancy within 3 years are eligible. The dual primary endpoints are real-world event free survival (rwEFS) defined as date from randomization to date of the first of the following events: failure to undergo resection for any reason, progression prior to surgery that precludes resection, recurrence or progression at any time after surgery or death from any cause, and overall survival (OS) defined as time from randomization to death from any cause. The target accrual is 1,100 patients assuming one-sided type I error of 0.03 for OS endpoint and 0.02 for rwEFS endpoint. This sample size will enable the detection of a 3-year rwEFS improvement from 55% in the adjuvant therapy arm to 64% in the perioperative arm with an 84% power. This sample size would detect an HR of 0.73 (improvement in median OS from 8.1 to 11 years in favor of the perioperative arm, 5-year OS from 65% in the adjuvant arm to 73% in the perioperative arm, assuming exponential survival) with 83.6% power. The study has a pragmatic design with minimal data collection, reporting of adverse events that lead to discontinuation of therapy, hospitalization or death only. It allows providers to choose therapy per standard of care (FDA approved or on NCCN), includes patients with ECOG performance status 2, permits use of local laboratory testing and imaging studies and determination of recurrence/progression will be done by local treating physicians with no use of RECIST. Clinical trial information: NCT06632327 .