Difference In Overall Survival Research Articles

Kidney-sparing surgery has equivalent oncological outcomes to radical nephroureterectomy for ureteral urothelial carcinoma.

Kidney-sparing surgery (KSS) for upper tract urothelial cancer (UTUC) has gained increasing interest recently. However, there is limited contemporary data regarding the role of KSS in ureteral urothelial carcinoma. Therefore, we investigated the survival outcomes of ureteral urothelial carcinoma after KSS from a large prospective international UTUC registry. The Clinical Research Office of the Endourology Society-Urothelial Carcinomas of the Upper Tract (CROES-UTUC) Registry included UTUC patients who received KSS or radical nephroureterectomy (RNU) between 2014 and 2019. In this study, we included patients with ureteral UTUC only. Study outcomes included overall survival (OS), cancer-specific survival (CSS), upper tract recurrence-free survival (RFS), intravesical RFS, progression-free survival (PFS), and metastasis-free survival (MFS). Propensity score matching (PSM) was performed to balance the tumour features' differences between groups. Of 391 patients with ureteral UTUC, 309 (79.0%) received RNU, and 82 (21.0%) received KSS by ureteroscopy with laser ablation (n=28) or segmental resection (n=54). After PSM, there were no differences in OS (p=0.525), CSS (p=0.487), upper tract RFS (p=0.147), intravesical RFS (p=0.989), PFS (p=0.617), and MFS (p=0.336) between KSS and RNU. Both ureteroscopic ablation and segmental resection had similar OS, CSS, intravesical RFS, PFS, and MFS with RNU. Proximal ureteral UTUC had worse OS and CSS outcomes than other tumour locations following segmental resection. In patients with ureteral UTUC, no significant differences in long-term survival outcomes were observed between KSS and RNU. Proximal ureteral UTUC had worse survival outcomes over other tumour locations following segmental resection.

Impact of lymph node retrieval on prognosis in elderly and non-elderly patients with T3-4/N+ rectal cancer following neoadjuvant therapy: a retrospective cohort study

PurposeThe optimal number of lymph nodes to be resected in patients with rectal cancer who undergo radical surgery after neoadjuvant therapy remains controversial. This study evaluated the prognostic variances between elderly and non-elderly patients and determined the ideal number of lymph nodes to be removed in these patients.MethodsThe Surveillance, Epidemiology, and End Results (SEER) datasets were used to gather information on 7894 patients diagnosed with stage T3-4/N+ rectal cancer who underwent neoadjuvant therapy from 2010 to 2019. Of these patients, 2787 were elderly and 5107 were non-elderly. A total of 152 patients from the Longyan First Affiliated Hospital of Fujian Medical University were used for external validation. Overall survival (OS) and cancer-specific survival (CSS) were evaluated to determine the optimal quantity of lymph nodes for surgical resection.ResultsThe study found significant differences in OS and CSS between elderly and non-elderly patients, both before and after adjustment for confounders (P < 0.001). The removal of 14 lymph nodes may be considered a benchmark for patients with stage T3-4/N+ rectal cancer who undergo radical surgery following neoadjuvant therapy, as this number provides a more accurate foundation for the personalized treatment of rectal cancer. External data validated the differences in OS and CSS and supported the 14 lymph nodes as a new benchmark in these patients.ConclusionFor patients with T3-4/N+ stage rectal cancer who undergo radical surgery following neoadjuvant therapy, the removal of 14 lymph nodes serves as a cutoff point that distinctly separates patients with a favorable prognosis from those with an unfavorable one.

Frailty in patients with IDH-mutant gliomas: experience from a high-volume tumor center.

Gliomas are increasingly diagnosed in an aging population, with treatment outcomes influenced by factors like tumor genetics and patient frailty. This study focused on IDH-mutant gliomas and assessed how frailty affects 30-day readmission and overall survival (OS). We aimed to address a gap in understanding the impact of frailty on this specific glioma subtype. 136 patients with an IDH-mutant glioma between 2007 and 2021 were identified at our institution. High frailty was classified by scores ≥ 1 on the 5-factor modified frailty index (mFI-5) and ≥ 3 on the Charlson Comorbidity Index (CCI). Patient and tumor characteristics including age, sex, race, Karnofsky Performance Status (KPS), Body Mass Index (BMI), tumor type and location, type of operation, and therapy course were recorded. Outcomes measured included 30-day readmission and overall survival (OS). Analysis was conducted utilizing logistic regression and Kaplan-Meier curves. Of the 136 patients, 52 (38%) had high frailty: 18 with CCI ≥ 3, 34 with mFI-5 ≥ 1. High frailty correlated with increased BMI (CCI: 30.2, mFI-5: 30.1kg/m2), more neurological deficits (CCI: 61%, mFI-5: 56%), and older age at surgery (CCI: 63, mFI-5: 48years). Hospital readmission within 30days occurred in 8 (5.9%) patients. Logistic regression indicated no significant difference in 30-day readmission rates (CCI: p = 0.30, mFI-5: p = 0.62) or median OS between high and low frailty groups. However, patients treated at our institution with newly diagnosed tumors with high mFI-5 had a 6.79 times higher adjusted death hazard than those with low mFI-5 (p = .049). Our analysis revealed that CCI and mFI-5 were not significantly associated with 30-day nor OS. However, in patients with non-recurrent tumors, there was a significant association of mFI-5 with OS. Further study of frailty with larger cohorts is warranted to enhance prognostication of outcome after neurosurgical treatment.

Phase III Randomized, Placebo-Controlled Trial of Endocrine Therapy ± 1 Year of Everolimus in Patients With High-Risk, Hormone Receptor-Positive, Early-Stage Breast Cancer.

Phosphatidylinositol 3-kinase/AKT-serine threonine kinase/mammalian target of rapamycin (mTOR) pathway abnormalities contribute to endocrine resistance. Everolimus, an mTOR inhibitor, improved progression-free survival in hormone receptor-positive metastatic breast cancer (BC) when combined with endocrine therapy (ET). In this phase III randomized, placebo-controlled trial, we assessed the efficacy of everolimus + ET as adjuvant therapy in high-risk, hormone receptor-positive, human epidermal growth factor receptor 2-negative BC after adjuvant/neoadjuvant chemotherapy. Patients were randomly assigned 1:1 to physician's choice ET and 1 year of everolimus (10 mg orally once daily) or placebo stratified by risk group. The primary end point was invasive disease-free survival (IDFS) evaluated by a stratified log-rank test with the hazard ratio (HR) estimated by Cox regression. Subset analyses included preplanned evaluation by risk group and exploratory analyses by menopausal status and age. Secondary end points included overall survival (OS) and safety. Everolimus did not improve IDFS/OS when added to ET in patients with early-stage high-risk, hormone receptor-positive BC. One thousand and nine hundred thirty-nine patients were randomly assigned with 1,792 eligible for analysis. Overall, no benefit of everolimus was seen for IDFS (HR, 0.94 [95% CI, 0.77 to 1.14]) or OS (HR, 0.97 [95% CI, 0.75 to 1.26]). The assumption of proportional hazards was not met suggesting significant variability in the HR over time since the start of treatment. In an unplanned subgroup analysis among postmenopausal patients (N = 1,221), no difference in IDFS (HR, 1.08 [95% CI, 0.86 to 1.36]) or OS (HR, 1.19 [95% CI, 0.89 to 1.60]) was seen. In premenopausal patients (N = 571), everolimus improved both IDFS (HR, 0.64 [95% CI, 0.44 to 0.94]) and OS (HR, 0.49 [95% CI, 0.28 to 0.86]). Treatment completion rates were lower in the everolimus arm compared with placebo (48% v 73%) with higher grade 3 and 4 adverse events (35% v 7%). One year of adjuvant everolimus + ET did not improve overall outcomes. Subset analysis suggests mTOR inhibition as a possible target for patients who remain premenopausal after chemotherapy.

Impact of number of dissected lymph nodes on recurrence and survival following thoracoscopic segmentectomy for clinical stage I non-small cell lung cancer

ObjectiveThis study aimed to identify the impact of number of dissected lymph nodes during thoracoscopic segmentectomy on recurrence and survival of clinical stage I non-small cell lung cancer (NSCLC). Patients and methodsWe retrospectively analysed data from prospectively collected consecutive thoracoscopic segmentectomies conducted between June 2008 and September 2023 at a single institution. Kaplan-Meier analysis with log-rank test assessed OS. Fine-Gray’s test assessed specific death in a competing risk model. The logistic regression model was utilized to predict recurrence, while the Cox regression model was employed to analyse overall survival (OS). Subgroup and sensitivity analyses were performed. ResultsA total of 227 patients were included in the final analyses. The mean follow-up was 38.4 months (standard deviation 35.8). Among all patients, 37 patients (16.3 %) experienced recurrence and 51 (22.5 %) deceased during the follow-up period. The median number of dissected lymph nodes was 9 (interquartile range (IQR) 6–12). No statistical difference in recurrence rate and 5-year OS was observed between cases with dissected lymph nodes > 9 and ≤ 9 (14.6 % vs. 17.6 %, p = 0.549; 75.5 % vs. 69.5 %, p = 0.760). On multivariable analysis, body mass index (odds ratio [OR] 1.15, p = 0.002), Charlson Comorbidity index (OR 1.28, p = 0.002), synchronous pulmonary cancer (OR 3.05, p = 0.019), and tumour size (OR 1.04, p = 0.044) increased of the recurrence rate, while percentage of predicted forced expiratory volume in 1 s (hazard ratio (HR) 1.09, p = 0.048), history of smoking (HR 1.02, p = 0.009), and solid nodule (HR 1.56, p = 0.010) was related to poorer survival. ConclusionsIn this study, number of dissected lymph nodes did not impact recurrence rate or overall survival after thoracoscopic segmentectomy for clinical stage I NSCLC.

Clinical, histopathological, and molecular biomarkers in a multicentric cohort of Mexican women with triple-negative breast cancer.

e13152 Background: Triple negative breast cancer (TNBC) is a heterogeneous entity with a marked variation in biological behavior, treatment responses, and patient outcomes. Thus, the investigation of clinical, histopathological, and molecular biomarkers is essential to understand this variability and potentially inform more effective management approaches across different patient profiles. Methods: We conducted a retrospective multicenter study of women &gt;18 years diagnosed with TNBC between 2006 and 2021 in two Mexican centers. We systematically gathered clinical and histopathological data, including an assessment of H&amp;E-stained slides for histopathological features and tumor-infiltrating lymphocytes (TILs), alongside immunohistochemistry analyses for androgen receptors (AR), CD8, and doublecortin-like kinase 1 (DCLK1). Statistical analyses were conducted using R version 4.3.2. Results: In our cohort, comprising 289 patients, the average age at diagnosis was 49.13 years, with a median overall survival (OS) of 63 months and a 5-year OS rate of 55%. The distribution of clinical stages at diagnosis was as follows: I (n=12, 4.2%), II (n=94, 32.5%), III (n=130, 45.0%), and IV (n=53, 18.3%). CD8 expression was higher in patients with no recurrence compared to patients with stage IV at diagnosis (p&lt;0.001), and it decreased with advancing clinical stages. We also found statistically significant differences in OS between negative and positive CD8 expression, favoring the latter (5-year OS 51.8% vs. 72.2%, p=0.032). Disease-free survival (DFS) and OS also differed significantly between low (≤10%) and high (&gt;10%) stromal TILs, favoring the high expression group (5-year DFS 51.9% vs. 70.8%, p=0.0066; 5-year OS 50.1% vs. 70.3%, p=0.0018). CD8 levels positively correlated with stromal and intratumoral TILs. Positive AR expression (&gt;10%) was seen in 8.9% of cases, with no observed differences in DFS or OS according to negative or positive status (5-year DFS 56.0% vs. 72.2%, p=0.42; 5-year OS 55.0% vs. 60.3%, p=0.68). Finally, DCLK1 positivity (≥10%) was seen in 23% of cases, with no influence on survival (negative vs. positive status, 5-year DFS 58.5% vs. 53.8%, p=0.63; 5-year OS 54.6% vs. 58.1%, p=0.60). Conclusions: Our study underscores the prognostic significance of CD8 and TILs in predicting DFS and OS among TNBC patients. Notably, the expressions of AR and DCLK1 were not independently associated with survival, although their prognostic impact in combination with other biomarkers is still an area of active research. Overall, our findings advocate for a more detailed examination of the molecular characteristics of TNBC within our demographic, encompassing an expanded array of biomarkers and a thorough investigation of the tumor microenvironment.

Neoadjuvant chemotherapy versus surgery plus adjuvant chemotherapy for locally advanced colon cancer: A meta-analysis of randomized controlled trials.

e15631 Background: The primary treatment for colon tumors is surgical resection, but the use of neoadjuvant chemotherapy (NAC) in managing locally advanced cases remains a subject of ongoing debate. We conducted a thorough meta-analysis, including randomized clinical trials (RCTs), to assess the oncological safety of neoadjuvant chemotherapy (NAC) in colorectal tumor patients. Methods: We systematically searched in PubMed, Scopus, Google Academic and Cochrane Library in January 2024 for studies that directly compared NAC versus surgery in patients with T3-4, N0-2, M0 colorectal cancer. We assessed overall survival (OS) and disease-free survival (DFS). We calculated odds ratios (ORs) and hazard ratios (HRs) using generic inverse variance in Review Manger 5.4. Heterogeneity was assessed using I² statistics. Results: We included seven RCTs, involving 4,391 patients. Among them, 53.5% underwent NAC, with a median age of 61.41 years and an average follow-up of 62.35 months. The comprehensive analysis revealed no statistically significant differences in 3-year OS (OR: 1.20, 95% CI: 0.91 to 1.59, p = 0.20), more than 2 years DFS (OR: 0.88, 95% CI: 0.37 to 2.13, p = 0.78) and five-year DFS (OR: 1.09, 95% CI: 0.83 to 1.43, p = 0.55). Employing a time-to-effect modeling approach, there was no significant difference in OS (HR: 1.04, 95% CI: 0.63 to 1.70, p = 0.88) or DFS (HR: 0.86, 95% CI: 0.7 to 1.06, p = 0.16); (Table 1). Conclusions: Our systematic review and meta-analysis of seven RCTs showed that neoadjuvant chemotherapy compared with surgery followed by adjuvant chemotherapy had similar overall survival and disease-free-survival in patients with locally advanced colon cancer. [Table: see text]

Impact of DNA damage repair alterations on real-world response to therapy in metastatic colorectal cancer.

e15557 Background: Alterations in the DNA damage repair (DDR) pathway genes contribute to tumor development. These alterations can be exploited by cytotoxic chemotherapy regimens that induce DNA damage. Platinum chemotherapy agents have been shown to be particularly effective in breast and ovarian cancer patients with alterations in the DDR pathway. However, the clinical impact of DDR alterations in metastatic colorectal cancer (mCRC) is still poorly understood. In this study, we utilize a large national database to evaluate clinical outcomes in patients with mCRC and alterations in DDR pathway genes. Methods: We reviewed 5602 patients that received standard fluorouracil based first-line chemotherapy regimens for mCRC using the nationwide Flatiron Health EHR-derived de-identified database. Chemotherapy regimens were categorized as a platinum-based doublet (FOLFOX, CAPOX), irinotecan-based doublets (FOLFIRI), or triplet (FOLFOXIRI). Overall survival (OS) was summarized within groups via Kaplan-Meier survival estimates. OS was compared between groups in the context of univariable and multivariable Cox proportional hazards models controlling for age, gender, DDR status, stage at diagnosis, ECOG, RAS/RAF status, MMR status, albumin and CEA at diagnosis. OS was defined as the time in months between date of first line therapy initiation to death. Results: DDR gene alterations were indentified in 35.7% (2001) patients.The most frequent mutations were in ATM (13.3%) and BRCA2 (8.3%). There was no significant difference in OS based on DDR mutation status. Within DDR altered patients, there was no difference in OS between those who received a platinum-based doublet, irinotecan-based doublet or triplet first-line therapy. Time to next treatment or death (TTNTD) was significantly improved with an irinotecan-containing doublet regimen and triplet regimen compared to a platinum-based doublet in a multivariable model (HR 0.79, p = 0.001 and HR 0.68, p = 0.002, respectively). There was no difference in OS in DDR-mutated patients that received an irinotecan-based regimen in the first line followed by an oxaliplatin-based regimen in the second line or the reverse sequence. When evaluating the impact of commonly co-mutated genes on survival we observed a worse OS in patients with a KRAS mutation in addition to a DDR mutation (HR 1.19, p = 0.045). An APC mutation was associated with an improved OS in the entire cohort, regardless of DDR status (HR 0.76, p &lt; 0.001). Conclusions: In this real-world population, approximately one third of patients with mCRC harbored an alteration in a DDR pathway gene. In these patients, TTNTD was greater with irinotecan-containing first line therapies (doublet or triplet). However, OS was similar regardless of which first-line chemotherapy was used.

Impact of race/ethnicity on the MammaPrint genomic assay risk and prognosis in early breast cancer (EBC): A National Cancer Database (NCDB) analysis.

564 Background: The 21-gene Oncotype DX Recurrence Score (RS) and 70-gene MammaPrint (MP) assays provide prognostic information for distant recurrence and are used to guide chemotherapy use in hormone receptor (HR)-positive, HER2-negative EBC. Previous reports have demonstrated that Black women with low genomic risk (RS 0-25) have a higher recurrence risk than White women in the TAILORx (PMID: 32986828) and RxPONDER trials (SABCS 2023, abstract GS1-01), and that Black race was associated with worse overall survival (OS) in multivariate models including RS in the NCDB registry (PMID: 33649322).The goal of this study was to evaluate the impact of race/ethnicity on MP risk distribution and prognostic information provided by the MP assay in the NCDB cohort. Methods: Women with HR-positive EBC with tumor size up to 5 centimeters (T1-T2), 0-3 involved lymph nodes (LNs, N0-N1), diagnosed between 2009-2018, and who had available information on MP testing and OS in the NCDB 2019 dataset were identified. Patients (pt) were stratified by MP result of high or low risk. T-tests and chi-square tests were used to compare pt characteristics, while log-rank tests assessed differences in OS between the high- and low-risk MP groups, as well as across different racial/ethnic categories. Results: 6096 eligible women were included of whom 41.0% (N=2502) were MP high-risk and 59.0% (N=3594) MP low-risk. Overall, 82.7% of pts were Non-Hispanic White (NHW), 8.7% Non-Hispanic Black (NHB), 4.7% Hispanic (H), and the remainder other/unknown (O). A higher proportion of H and NHB pts had high MP results, p&lt;0.0001. The MP high-risk group had a greater proportion of pts &lt;/= 50 years (p=0.0013) and larger tumors (p&lt;0.0001) and higher grade (p&lt;0.0001), but not LN positive (p=0.7649). The 5-year OS rates (and 95% Confidence Intervals) for the MP high and low-risk groups were 92.6% (91.6% - 93.7%) and 96.6% (95.9% - 97.2%), respectively, p&lt;0.0001. There were no differences in OS based on race/ethnicity in the low-risk group with 5-year OS rates of 98.4% (96.1%-100%), 95.9% (93.3% - 98.6%), 96.4% (95.7% - 97.1%), and 99.2% (97.7% - 100%) for H, NHB, NHW and O, respectively, p=0.34. Similarly, in MP high-risk, race/ethnicity did not impact prognosis with OS rates of 92.6% (88.2% - 97.1%), 90.8% (87.2% - 94.5%), 92.8% (91.7% - 94.1%), and 95.8% (91.2% - 100%) for H, NHB, NHW and O groups, respectively, p=0.45. There was no significant interaction between race and MP for OS when accounting for age, tumor grade, tumor size, and LN status, p=0.75. Conclusions: NHB and H women were more likely to have high-risk MP results compared with NHW women in this NCDB cohort, although race/ethnicity did not impact prognosis for 5-year OS in either MP risk group. Limitations of this analysis include absence of information on recurrence and short follow up, as about one-half of recurrences in HR-positive EBC occur after 5 years.

A single center retrospective cohort study of patients with metastatic breast cancer and leptomeningeal disease: Updated survival data and subgroup analyses by breast cancer subtype.

1108 Background: Patients (pts) with metastatic breast cancer (MBC) and leptomeningeal disease (LMD) have a poor prognosis with limited therapies. We previously reported data from our retrospective LMD registry; here we provide an update with additional pts and subgroup analyses highlighting differences in treatment and survival by breast cancer subtype. Methods: In this single center retrospective cohort study, we identified pts with MBC and LMD who received care from 2000-2024 and abstracted key clinical, treatment, and overall survival (OS) data. Results: We identified 111 pts with MBC and LMD, including pts with the following subtypes: HR+/HER2- (n=53, 47.7%), HER2+ (n=30, 27.0%), and triple negative breast cancer (TNBC; n=28, 25.2%). The majority of pts had concurrent brain metastasis (n=82, 73.9%). Median time from diagnosis of MBC to LMD was 16.4 months (mo) (range 0-101.3 mo). Pts received a median of 3 lines of therapy prior to the diagnosis of LMD (range 0-10) and 1 line after the diagnosis of LMD (range 0-4). Most pts received central nervous system-directed (CNS)-directed therapy (n=94, 84.7%), including intrathecal (IT) therapy (n=42, 37.8%) and/or CNS radiation (n=70, 63.1%). Median OS from the diagnosis of LMD to death was 4.1 mo (range 0.1-78.1 mo) and varied by subtype, with pts with HR+/HER2- or HER2+ MBC and LMD living longer than those with TNBC and LMD (4.2 and 6.8 mo respectively vs. 2.0 mo, p&lt;0.01, HR 2.15, 95% CI 1.36-3.39). There was no difference in OS by histology ductal vs. lobular or by presence or absence of concurrent parenchymal brain metastases. Pts who received IT therapy survived longer than those who did not (7.1 vs. 2.7 mo, p=0.01, HR 0.60, 95% CI 0.40-0.90). There was difference in OS by receipt of CNS-directed radiation therapy. Pts diagnosed with LMD from 2015-2024 lived longer than those diagnosed from 2000-2014 (6.4 vs. 2.9 mo, p=0.04, HR 0.67, 95% CI 0.46-0.99). On multivariable analysis, having TNBC was associated with shorter OS from time of LMD to death (p=0.004, HR 2.03, 95% CI 1.25-3.30). Conclusions: This study represents one of the largest case series of pts with MBC and LMD, including the most pts diagnosed after 2015 to our knowledge. Pts with lobular histology, HER2+ BC, TNBC, and those with de novo MBC were over-represented compared to the general MBC population. Pts with HR+/HER2- or HER2+ disease, LMD diagnosed after 2015, and those who received IT therapy survived longer than their respective cohorts. Novel diagnostic and therapeutic strategies for pts with MBC and LMD remains an area of unmet clinical need.

Novel HLA-Ilo/HLA-IIhi phenotype and immune evasion in triple-negative breast cancer.

1095 Background: Immune checkpoint inhibitors (ICIs) are a therapeutic option for patients with triple-negative breast cancer (TNBC), however resistance and non-response remain an unmet clinical need. Human leukocyte antigens (HLAs) play an important role in induction and regulation of host immune responses. Downregulation of HLA class I expression is one mechanism by which cancer cells evade the immune control. HLA typing and understanding the role of HLAs can provide valuable insight into optimizing immunotherapy efficacy in TNBC. In this study, we evaluate the association of HLA I/II phenotypes with biomarkers of tumor immune interaction and overall survival (OS) in a real-world breast cancer cohort. Methods: A targeted RNA-seq assay was performed on 142 breast cancer samples. HLA I and HLA II expressions were estimated as average expression of HLA-A, HLA-B, HLA-C and HLA-DP, HLA-DQ, HLA-DR genes, respectively, by a percentile rank values [0-100]. Cohen D index was used to estimate ratio of HLA-I and II in each specimen. We particularly focused on the HLA-Ilow(lo)/HLA-IIhigh(hi) ratio given a proposed mechanism of immune escape by tumor cells (low expression of HLA-I) in response to a highly immune infiltrated state where there is increased expression of HLA-II by the immune cells. We studied the co-expression of HLA-Ilo/HLA-IIhi with other checkpoint targets using Spearman correlation(rs). The impact of HLA phenotypes on OS were analyzed using Kaplan-Meier analysis and Chi-squared assessed associations. Results: The cohort consisted of 106 non-TNBC (ER+/HER2- or HER2+) and 36 TNBC tumors. Most samples originated from metastatic visceral sites (96, 68%) followed by primary breast (33, 23%), and lymph nodes (13, 9%). Among TNBC, HLA-Ilo/HLA-IIhi phenotype displayed a significantly higher co-expression of immune checkpoint targets such as PD-1, PD-L1, TIM3 and LAG-3 than HLA-Ihi/HLA-IIlo phenotype (p&lt;0.001). However, this difference was not observed between HLA-Ilo/HLA-IIhi and HLA-Ihi/HLA-IIlo phenotypes in non-TNBC tumors. In TNBC, there was no significant difference in OS between HLA-Ilo/HLA-IIhi when compared to HLA-Ihi/HLA-IIlo (43 vs. 37 months, p=0.21). Similarly, in non-TNBC, there were no significant differences in OS between HLA-Ilo/HLA-IIhi when compared to HLA-Ihi/HLA-IIlo (107 vs. 66 months, p=0.5). Conclusions: Concurrent loss of HLA I with increased HLA II expression was associated with co-expression of immune checkpoint molecules indicative of immune escape mechanism but not survival outcomes in TNBC. This same effect was not seen in non-TNBC with a more immunologically silent environment. Characterization of HLA phenotypes by immune profiling provides insight into the complex interplay of tumor immune microenvironment and offers an opportunity for developing novel approaches to overcome the immune evasion with cancer vaccines and adoptive cell therapies in TNBC.

Disparities in patients with HER2-positive breast cancer receiving optimal treatment: Analysis of the real-world ASCO CancerLinQ dataset.

e13739 Background: Racial/ethnic disparities in locoregional second breast cancer events (SBCE) in patients (pts) with HER2-positive (HER2+) breast cancer (BC) are not well defined. We examined rates of SBCE and overall survival (OS) by race and ethnicity in the ASCO CancerLinQ Discovery (CLQD) real-world dataset in HER+ BC pts receiving optimal and not-optimal treatment. Methods: CLQD was used to identify pts undergoing surgery for stage I-III HER2+ BC from 2005-2022. Race/ethnicity were self-reported. Optimal treatment was defined as HER2-directed therapy for stage II-III HER2+ BC starting in 2008, adjuvant endocrine therapy for hormone-receptor positive (HR+) HER2+ BC, radiation after lumpectomy, and regional nodal irradiation for N2-N3 disease. The primary endpoint was SBCE defined as a second event in the ipsilateral or contralateral breast or axilla, with OS as a secondary endpoint. Kaplan-Meier analysis was used to estimate SBCE-free survival and OS. Results: Of 8,795 stage I-III HER2+ BC pts, 5,487 (62.4%) were Non-Hispanic White (NHW), 1,083 (12.3%) Non-Hispanic Black (NHB), 418 (4.7%) Hispanic, 323 (3.7%) Asian or Pacific Islander (API), and 1,484 (16.9%) other/unknown. Overall, 39.2% had HR-HER2+ and 60.7% had HR+HER2- BC. NHW pts were the most likely to present with stage I disease (40.2% vs 31.9%, 29.0%, and 30.3% of NHB, Hispanic, and API pts, respectively, p&lt;0.01) and less likely to be age &lt;50 at diagnosis (26.1% vs 32.3%, 41.0%, and 36.6% in NHB, Hispanic, and API, p&lt;0.01). Overall, 54.2% of HER2+ BC pts received optimal treatment: 54.1%, 60.2%, 60.5%, and 58.8% of NHW, NHB, Hispanic, and API pts (p&lt;0.01). Neoadjuvant HER2-therapy was given in 42.4%, 46.3%, 53.8%, and 51.2% of NHW, NHB, Hispanic, and API pts (p&lt;0.01) and endocrine therapy in 64.7%, 56.8%, 59.3%, and 54.7%, respectively (p&lt;0.01). 5-yr SBCE-free survival and OS are shown (Table). SBCE-free survival was not statistically different by race and ethnicity in optimally or non-optimally treated pts. Optimal treatment increased OS by 4.1% and 0.9% in NHW and NHB pts with HR-HER2+ BC and 2.4% and 8.9% in NHW and NHB pts with HR+HER2+ BC. Conclusions: Differences in OS, but not SBCE, were seen by race/ethnicity in HER2+ BC. OS differences were not completely mitigated by receipt of optimal treatment. [Table: see text]

The prevalence of sickle cell phenotype and its association with clinical outcomes in patients with solid malignancies.

10563 Background: Sickle cell disease (SCD) is the most common inherited blood disorder in the United States and is caused by a mutation of β-globin ( HBB-Mt). The risk of developing solid malignancies in this population remains controversial, with research showing increased rates of some solid tumors (colon, kidney, and thyroid) and decreased rates of others (breast and male genitourinary). We report the prevalence of HBB mutations across a cohort of solid tumors and clinical outcomes between HBB-Wild type (-Wt) v Mutant (-Mt) tumors. Methods: Non-small cell lung cancer (NSCLC, N = 3307), breast (BC, N = 1960), colorectal (CRC, N = 2161), prostate (N = 899), and gynecologic cancers (N = 2,805) in persons of African descentwere tested at Caris Life Sciences (Phoenix, AZ) with NextGen Sequencing of DNA (whole exome) and RNA (whole transcriptome). Her2/Neu (+: ≥3+ and &gt;10%) and HR (ER or PR+: ≥1+ and ≥1%) expression was tested by immunohistochemistry. Tumors were assessed for single nucleotide variations (SNVs) and insertions/deletions (indels) in HBB associated with a sickle cell phenotype. Mutation prevalence for all other genes was calculated for pathogenic SNVs/indels. Differentially regulated pathways were assessed by gene set enrichment analysis (GSEA). Fisher’s Exact/χ2 tests were applied as appropriate with p-values adjusted for multiple comparisons ( p &lt; .05). Real-world overall survival (OS) and ethnicity data was obtained from insurance claims and log-rank estimates were calculated for molecularly defined subpopulations. Results: Amongst persons of African descent, uterine sarcoma had the highest prevalence of HBB-Mt (17.1%, 43/251) followed by uterine serous carcinoma (9.1, 70/768) and endometrial carcinoma (7.8, 55/708). Tumors with the highest absolute number of HBB-Mt tumors were NSCLC (7.0, 230/3307), CRC (8.1, 176/2161) and BC (6.7, 131/1960). In CRC, there was no significant difference in the prevalence of right-sided tumors between HBB-Wt v Mt (42% v 51, p = .06), nor in the prevalence of HBB-Mt by consensus molecular subtype ( p = .34). No significant enrichment of HBB-Mt across BC subtypes was observed (HR- HER2-: 7.8%, HR-HER2+: 9.7, HR+/HER2-:5.8, HR+/HER2+: 8.1, p = .34). No difference in the prevalence of pathogenic alterations was observed between HBB-Mt vs -Wt across NSCLC, CRC, and BC ( p &gt; .05). HBB-Mt NSCLC were significantly enriched (GSEA) for genes related interferon /, inflammatory response and IL6/JAK/STAT3. No significant difference in OS was observed in CRC (median survival HBB-Wt: 957 days v -Mt: 1034, p = .43), NSCLC (-Wt: 591 v -Mt: 648, p = .59) or BC (-Wt: 924 v -Mt: 922, p = .61). Conclusions: No significant differences in the genomic landscape nor in OS of HBB-Mt vs HBB-Wt NSCLC, CRC or BC were observed. NSCLC HBB-Mt was enriched with inflammatory response genes. Future work should focus on potential role HBB-Mt plays in NSCLC.

Chemotherapy and liver transplantation versus chemotherapy alone in patients with definitively unresectable colorectal liver metastases: A prospective multicentric randomized trial (TRANSMET).

3500 Background: Despite the increasing efficacy of chemotherapy (CT) and advances in surgical techniques for initially unresectable colorectal liver metastases (uCLM), secondary resection rate remains low. For definitively uCLM, CT remains the standard of care but liver transplantation (LT) has shown promising results. This first randomized trial aimed to assess the efficacy of CT combined to LT for uCLM. Methods: Patients with definitively uCLM from resected BRAF non mutated colorectal cancer, having responded to CT (≥ 3 months and ≤ 3 lines) in the absence of extrahepatic disease, were validated by an independent experts’ committee and randomly assigned (1:1) to receive CT and LT (CT+LT arm) or CT alone (CT arm). The primary endpoint was 5-year overall survival (OS). Secondary endpoints were progression free survival (PFS) and patterns of recurrence. In order to detect a 40% difference in OS from 10% (CT) to 50% (CT+LT) (2-sided α level 5% - 90% power), 29 events were initially needed, secondly re-estimated to 50 according to the rate of patients not receiving LT in the CT+LT arm during the study. Results: Between February 2016 and July 2021, 94 patients (median age 54 years, IQR 47-59) were randomly assigned to CT+LT arm (n = 47) or CT arm (n = 47). Median number and maximal diameter of uCLM at diagnosis were 20 (13-25) and 51.5 (37-78) mm, respectively. At randomization, objective response was obtained after a median number of 20 (14-27) CT cycles during 1 (44%), 2 (40%) or 3 (16%) lines. Median delay between primary tumour resection and randomisation was 14.6 (10.6-22.3) months. In CT+LT arm, 38 (81%) underwent LT after a median of 51 (30-65) days from randomization. Nine patients did not receive LT because of tumour progression during the waiting time or intraoperative finding of extrahepatic disease. Three (8%) of the 38 transplanted patients were retransplanted, one of whom (3%) died postoperatively. Post-transplant CT was administered in 26 (68%) patients. In CT arm, 9 (19%) patients unexpectedly underwent partial hepatectomy (7) or LT (2). In intent-to-treat analysis, 5-year OS was 57% in CT+LT arm and 13% in CT alone arm (log-rank test: p = 0.0003 - HR 0.37; 95%CI 0.21-0.65). In per protocol analysis, 5-year OS rate was 73% and 9%, respectively (HR 0.16; 95%CI 0.07-0.33). Median PFS was 17.4 months versus 6.4 months (HR 0.34; 95%CI 0.20-0.58), respectively. Among transplanted patients, 28 (74%) had lung (39%), liver (3%), other (21%) or multisite (11%) recurrence, optionally treated by surgery (36%) or local ablation (11%). Fifteen (40%) patients were ultimately disease-free. Conclusions: LT combined with CT significantly improved survival in selected patients with uCLM compared to CT alone. These results argue for validating LT as a new standard option that may change the treatment strategy for liver-only uCLM patients. Clinical trial information: NCT02597348 .

Survival benefit with regorafenib and/or trifluridine/tipiracil sequencing to rechallenge with anti-EGFR-based third-line regimens in metastatic colorectal cancer: A multicenter retrospective real-world subgroups comparison.

e15553 Background: Rechallenge with anti-EGFR drugs has recently proven therapeutic activity in a subset of RAS wild type (wt) metastatic colorectal cancer (mCRC) patients who had previously benefited from cetuximab- or panitumumab-based first-line regimen. Regorafenib (R) and Trifluridine/tipiracil (T) have been found to improve survival in patients with refractory mCRC. This real-life subgroup survival analysis focused on treatment with R and T, sequential or not, in patients who had received prior third-line anti-EGFR therapy. Methods: Clinical data of patients diagnosed with mCRC who received R and/or T between July 2012 and March 2022, were retrospectively collected from 13 Italian cancer institutes. The objective of this subgroup analysis was to compare overall survival (OS) and progression-free survival (PFS) in patients who received late-line R and/or T according to prior third-line anti-EGFR-based treatment. Results: The entire study enrolled 866 patients. 146 (16.8%) of them received the T/R sequence (T/R), 116 (13.3%) the reverse sequence (R/T), 325 (37.5%) T, and 279 (32.5%) R. For the purpose of this subgroup analysisi we identified 338 RAS wt patients (39%) who were eligible. Of these, 290/338 patients (85.8%) did not receive the previous third-line anti-EGFR therapy, while 48 patients (14.2%) did it (12 T/R, 10 R/T, 13 T, 13 R). When comparing T/R to R/T in patients who did not previously received third-line anti-EGFR drug rechallenge, we observed a statistically significant and clinically meaningful improvement in PFS. In detail, the median PFS benefit was 67,5% when treating patients with T/R sequence vs. the reverse sequence (11,4 vs. 3,7 months, respectively, ∆ = 7,7 months; p = &lt; 0,0001; HR = 0,17; 95% CI = 0,09-0,32). In patients who received T/R or R/T following rechallenge with anti-EGFR drug, we also observed a comparable, albeit smaller and non-statistically significant, improvement in PFS (8.1 vs. 7.8 months, respectively; p = 0.22; HR 0,51; 95% CI = 0,17-1,50). There were no statistically significant differences in OS between these groups. Anti-EGFR rechallenge data analysis showed that the non-sequential administration of R and T had no statistically significant impact on survival outcomes. Conclusions: With the limit of the sample size, our retrospective subgroup analysis failed to validate the promising beneficial effects of anti-EGFR rechallenge prior to R and/or T treatment. A statistically significant longer PFS was only observed in patients with refractory metastatic colorectal cancer receiving T/R sequence without prior cetuxumab- or panitumumab-based regimens.

Overall survival in patients with HER2-low breast cancer at a reference hospital in Mexico.

e12578 Background: Breast cancer is the most diagnosed cancer in women. The 5-year overall survival (OS) rate in early-stage disease is 97% while in advanced disease is 36%. HER2 is a growth receptor involved in cell survival and proliferation. An overexpression of this protein leads to a more aggressive behavior; however, with targeted therapies, OS has improved. Recently, a new classification has been developed for tumors previously known as HER2-negative: HER2-low; which are those with IHC 1+ or 2+/ISH negative. It is believed that in these types of tumors, the signaling pathways of the HER2-positive subtype are also activated. There are conflicting studies on the prognostic impact of this subgroup. Currently, there is availability of anti-HER2 treatment for patients in advanced stages, as described in the DESTINY-Breast04 study, which changes the treatment paradigm for this pathology. Methods: The aim of this study is to determine overall survival in patients with HER2-low breast cancer. A retrospective, analytical, observational cohort was performed. Patients diagnosed with HER2-negative/low breast cancer, treated at the UMAE Oncology Hospital of the CMN Siglo XXI, from January 2018 to December 2022, were included. OS and disease-free survival (DFS) were calculated using Kaplan-Meier curves, and the impact of HER2-low expression on OS and DFS was assessed using log-rank analysis. The prognostic analysis of the complete model was performed using a Cox proportional hazards model. Results: We included 213 patients. The median age was 57 years. Ninety-five patients were HER2-low (44.6%), and 118 were HER2-negative (55.4%). Seventy-six percent had positive hormone receptor (HR) status. Patients with HR+/HER2-negative were 84 (52.2%), and HR+/HER2-low were 77 (47.8%). Among HR-negative status, the majority were HER2-negative (65.4%). When comparing HER2-negative and HER2-low, no statistically significant differences were found, with a 48-month overall survival of 70% for HER2-negative compared to 87.1% for HER2-low (p= 0.5700). OS analysis in the HER2-low group, comparing HR+ vs. HR-, a statistically significant difference at 48 months of 98.31% vs. 49.17% (p &lt;0.0001), respectively, was found. Regarding DFS, a comparison between HR+ against HR-, it was 79.53% vs. 37.14%, respectively (p= 0.0002). The DFS analysis revealed that, among the variables studied, lymphovascular invasion (LVI) and HR+ status showed a statistically significant association with time to recurrence. Particularly, the presence of HR positivity was associated with a significant 82.6% reduction in the risk of recurrence. Conclusions: HER2 status alone (negative or low) did not offer a clear distinction in terms of OS or DFS. Nevertheless, it was observed a difference in OS and DFS outcomes favoring the HR-positive group when examining HR status among individuals with HER2-low, though this finding requires validation in a larger population.

Racial disparities in the immunotherapeutic outcomes of patients with non-small cell lung cancer (NSCLC): An in-depth systematic review and meta-analysis.

1579 Background: The utilization of immunotherapy has become prevalent in the therapeutic approach to non-small cell lung cancer (NSCLC), owing to its association with enhanced survival outcomes. Nevertheless, a notable gap exists in the available information regarding potential variations in the survival benefits of immunotherapy based on the racial demographics of NSCLC patients. Methods: A systematic search for articles published until January 2023 was performed on PubMed, EMBASE, and Google Scholar databases. Articles that aligned with the research objective were included, while non-English articles, case reports, conference abstracts, studies combining immunotherapy with other cancer therapies, and studies on small-cell lung cancer were excluded. Data required for review and analysis was independently abstracted into separate Excel files by two reviewers. Furthermore, Statistical analyses were performed using the Review Manager software, and the methodological quality evaluation was done using the Newcastle Ottawa Scale. Results: Seven cohort studies were used for review and analysis. A subgroup analysis of data from these studies showed that Black/African American and Asian NSCLC patients receiving immunotherapy had improved overall survival (OS) than White patients (HR: 0.84; 95% CI: 0.75 – 0.95; p = 0.006 and HR: 0.53; 95% CI: 0.30 – 0.93; p = 0.03, respectively). However, the difference in OS is statistically insignificant when Hispanic patients are compared with white patients (HR: 0.68; 95% CI: 0.46 – 1.00; p = 0.05). On the other hand, the subgroup analyses did not demonstrate any significant difference in progression-free survival (PFS) when comparing Black/African American, Asian or Hispanic patients to White patients (HR: 0.93; 95% CI: 0.79 – 1.09; p = 0.35, HR: 0.89; 95% CI: 0.51 – 1.55; p = 0.69, and HR: 1.01; 95% CI: 0.82 – 1.23; p = 0.96, respectively). Conclusions: Among non-small cell lung cancer (NSCLC) patients undergoing immunotherapeutic interventions, it is discerned that Black/African American and Asian individuals exhibit superior overall survival (OS) outcomes compared to their White counterparts. However, it is noteworthy that the observed racial disparity does not appear to exert a discernible influence on the progression-free survival (PFS) of NSCLC patients subjected to immunotherapy.

Evaluating disparities in receptor status, overall survival, and time to hormone therapy among women with breast cancer.

11096 Background: Breast cancer receptor status (ER/PR/HER2) is essential to guide treatment decisions. However, national race/ethnicity subtype studies rarely include Indigenous American Indian and Alaska Native (AI/AN) and Native Hawaiian and other Pacific Islander (NHPI) women. This study aims to compare across race/ethnicity: 1) hormone receptor (HR)/HER2 status, 2) Overall Survival (OS) for Triple Positive breast cancer, and 3) Time to Hormone Therapy (THT). Methods: A cohort study of women with breast cancer (Stage 1-4), age ≥18 years, diagnosed 2004-2017 was conducted with the National Cancer Database. Race was used as federally defined (White, Black, Asian, AI/AN, and NHPI) with Hispanic ethnicity. Primary endpoints were receptor status, OS, and THT (days from diagnosis to hormone therapy). Kaplan-Meier estimates and log-rank tests assessed OS. Multivariable logistic, Cox Proportional Hazard, and linear regression evaluated the likelihood of HR+/HER2+ (adjusted Odds Ratio [aOR]), death (adjusted Hazard Ratio [aHR]), and THT in days (adjusted β [aβ]), respectively, with 95% confidence intervals (95%CI). The majority non-Hispanic White population served as reference. All regressions were adjusted for sociodemographic and cancer characteristics. All HER2 analyses used a subset of women diagnosed post-2010, given inconsistent testing pre-2010. Results: 1,812,911 women were included who mostly had Stage 1 cancer (53%), from metropolitan areas (84%), with private insurance (51%), and a median age of 61 (IQR 51-71) years. Women were 81% White, 11% Black, 5% Hispanic, 2% Asian, 0.3% AI/AN, and 0.2% NHPI. NHPI women had the highest ER+ (84%) and PR+ (75%) cancers, while Asian women had the highest HER2+ (18%). Adjusted for covariates, only NHPI women were significantly more likely to have HR+ cancer (aOR=1.3, 95%CI=1.2-1.5) while Black women were less likely (aOR=0.6, 95%CI=0.6-0.6), compared to White women. Hispanic women were significantly more likely to have Triple Positive cancer (aOR=1.1, 95%CI=1.1-1.2) while Black women were less likely (aOR=0.9, 95%CI=0.9-0.9). Median follow-up was 63 (IQR 36-101) months. Among women with Triple Positive breast cancer, there were significant differences in OS (p&lt; .0001) with 7-year survival ranging from 77% for NHPI women to 89% for Asian women. NHPI women had the highest risk of death (aHR=1.5, 95%CI=1.0-2.1), followed by AI/AN (aHR=1.5, 1.05-2.0), and Black (aHR=1.2, 95%CI=1.1-1.2). Adjusted for covariates, among women with HR+ breast cancer, longer THT occurred among Black (aβ=18 days, 95%CI=17-18), Hispanic (aβ=16 days, 95%CI=15-17), and NHPI women (aβ=14 days, 95%CI=9-18). Conclusions: NHPI women have higher HR+ rates while Black, Hispanic, and NHPI women with HR+ cancer experience longer times to hormone therapy. This is likely the first US analysis of breast cancer subtypes using federal race/ethnicity standards.

Vandetanib in locally advanced or metastatic differentiated thyroid cancer refractory to radioiodine therapy.

VERIFY study is a randomized, double-blind, multicenter phase III clinical trial aimed to determine the efficacy and safety of vandetanib in tyrosine kinase inhibitor-naive patients with locally advanced or metastatic differentiated thyroid cancer (DTC), refractory to radioiodine (RAI) therapy with documented progression (NCT01876784). Patients were randomized 1:1 to vandetanib or placebo. The primary endpoint was progression-free survival (PFS). Secondary endpoints included best objective response rate, overall survival (OS), safety, and tolerability. Patients continued to receive randomized treatment until disease progression or for as long as they were receiving clinical benefit unless criteria for treatment discontinuation were met. Following randomization, 117 patients received vandetanib and 118 patients received placebo. Median PFS was 10.0 months in the vandetanib group and 5.7 months in the placebo group (hazard ratio [HR] 0.75; 95% confidence interval [CI] 0.55-1.03; p = 0.080). OS was not significantly different between treatment arms. Common Terminology Criteria for Adverse Events [CTCAE] adverse events of grade ≥3 were reported in 55.6% of patients in the vandetanib arm and 25.4% in the placebo arm. Thirty-three deaths (28.2%; one related to study treatment) occurred in the vandetanib arm compared with 16 deaths (13.6%; two related to treatment) in the placebo arm. No statistically significant improvement was observed in PFS in treatment versus placebo in patients with locally advanced or metastatic, RAI-refractory DTC. Moreover, active treatment was associated with more adverse events and more deaths than placebo though the difference in OS was not statistically significant.

Racial differences in therapies received by patients with cutaneous T cell lymphoma (CTCL): A single center retrospective cohort analysis.

e23141 Background: Black patients with cutaneous T-cell lymphoma (CTCL) have increased risk of mortality and higher rates of treatment complications compared to other racial groups, however, drivers of these disparities are poorly understood. Recent advances in novel targeted therapies, such as mogamulizumab and brentuximab vedotin (BV), have demonstrated improved survival compared to standard therapies. We aimed to identify treatment patterns and clinical outcomes in patients with mycosis fungoides and Sezary syndrome (MF/SS) to better understand potential drivers underlying these racial disparities. Methods: We performed a retrospective review of 282 patients with a histopathologic diagnosis of advanced stage MF/SS seen at the Winship Cancer Institute of Emory University from 2000-2023. Clinical data was collected from the electronic medical record and included demographics, histopathologic findings, therapies received, highest disease stage reached, and survival. Differences in baseline characteristics and treatments were assessed using univariate analysis. The association between race, insurance status, disease stage, and category of treatment was assessed using multivariable analysis of overall survival (OS). Results: The cohort was comprised of an even distribution of patients identifying as Black (50%) and white (47.5%). Median age at diagnosis was 61 years (range, 12-91), and Black patients had an earlier age of diagnosis compared to white (median 52 vs. 65.5 years, p &lt; 0.001). The majority of patients had a pathological diagnosis of MF (79.1%). Large cell transformation was seen in 24.8%. Most common stage was stage 2b (36.2%); other stages included 3a (18.1%), 3b (4.3%), 4a1 (19.1%), 4a2 (13.1%), and 4b (9.2%). Systemic therapies were divided into three groups: standard chemotherapy, biologics (interferon, retinoids, extracorporeal photopheresis, and methotrexate), and novel agents (mogamulizumab, BV, and clinical trials). Median OS was 47.5 months (range, 2-246 months), and was greater in patients who received treatment with novel agents (hazard ratio 0.46, 95%, CI 0.29-0.73, p &lt; 0.001). Black patients were less likely to receive photopheresis and local radiation compared to white patients (36.73% vs. 63.27% and 39.53% vs. 60.47%, p &lt; 0.05, respectively), however, there were no differences in the receipt of novel agents by race. There were no differences in OS between Black and white patients. Conclusions: While we did find some differences in treatment patterns by race, these did not translate to a difference in outcomes. Importantly, in this cohort of patients who received similar rates of novel targeted therapies across racial groups, there were no differences in survival by race. These findings suggest that factors such as access to novel targeted therapies may play a role in the well-documented racial disparities in treatment outcomes.