Difference In Overall Survival Research Articles

Kidney-Sparing Surgery Has Equivalent Oncological Outcomes to Radical Nephroureterectomy for Ureteral Urothelial Carcinoma.

Introduction and Objective: 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. Methods: The Clinical Research Office of the Endourology Society-Urothelial Carcinomas of the Upper Tract (CROES-UTUC) Registry included patients with UTUC 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 tumor features' differences between groups. Results: Of the 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. There were no significant differences between ureteroscopic ablation and segmental resection in OS, CSS, intravesical RFS, PFS, and MFS with RNU. Proximal ureteral UTUC had worse OS and CSS outcomes than other tumor locations following segmental resection. Conclusions: 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 tumor locations following segmental resection.

Randomized phase II/III trial of gemcitabine plus nab-paclitaxel versus concurrent chemoradiotherapy with S-1 as neoadjuvant treatment for borderline resectable pancreatic cancer: GABARNANCE study.

LBA4014 Background: No randomized controlled trials have compared systemic chemotherapy and chemoradiotherapy as neoadjuvant therapy for borderline resectable pancreatic cancer (BRPC). We attempted to determine which of the two could become established as standard neoadjuvant therapy for BRPC. Methods: This was an open-label, multicenter, randomized controlled phase II/III trial comparing two neoadjuvant treatments (UMIN-CTR 000026858): gemcitabine (GEM) plus nab-paclitaxel (nab-P) (group A, GEM 1000 mg/m2 IV + nab-P 125 mg/m2 IV on days 1, 8, and 15, 2 cycles) and concurrent chemoradiotherapy (50.4 Gy/28 fractions) with S-1 (80 mg/m2) on the irradiation days (group B). After the neoadjuvant therapy, patients (pts) underwent surgical resection if R0/R1 resection was judged as being possible, followed by postoperative adjuvant S-1 therapy for 6 months. The key eligibility criteria included patients aged 20 to 79 years with histologically proven adeno(squamous)carcinoma, centrally confirmed BRPC, PS 0-1, and no prior treatment for BRPC. The primary endpoint of the phase III part was overall survival (OS). A total of 110 pts (65 events) was required to detect a 17% difference in the 2-year OS [hazard ratio (HR) of 0.70] with a two-sided alpha level of 10% and power of 70%. Results: A total of 112 pts were randomly assigned to the trial treatments between June 2017 and December 2022 (group A/B: 56/56 pts). The median OS was 23.1 months in group A and 31.5 months in group B. No statistically significant difference in the OS was observed between the two arms (HR 0.758, 95% CI: 0.472-1.219, p = 0.2518), but a large late separation of the Kaplan-Meier curves was observed after 18 months. The difference in the 2-year OS between the groups was 14.6% (group A: 48.2%, group B: 62.8%); the separation continued until the end of the observed survival curves. A similar late separation in the PFS was seen after around 12 months, but the difference in the PFS was not statistically significant (median PFS: Group A, 12.6 months, Group B, 11.1 months; HR 0.805; 95% CI: 0.535-1.212; p = 0.2565). The R0 resection rate did not differ between the two groups (group A, 60.7%; group B, 57.1%). The tumor response rate was higher in Group A (group A, 16.1%; group B, 8.9%), but the pathological response rate was higher in group B (group A, 14.3%; group B, 30.4%). Neutropenia and thrombocytopenia were observed more frequently in group A, while anorexia was observed more frequently in group B. Both treatments were well-tolerated. Conclusions: A delayed survival advantage, in terms of both the OS and PFS, of concurrent chemoradiotherapy with S-1 was observed, without any additional toxicity burden. An updated analysis with longer-term efficacy/toxicity data is planned to verify the advantage of neoadjuvant chemoradiotherapy. Clinical trial information: UMIN-CTR 000026858.

Prognostic value of liver metastases in colorectal cancer treated by systemic therapy: An ARCAD pooled analysis

BackgroundThe liver is the most frequent site of metastases in colorectal cancer (CRC). This study aimed to assess the response rate and survival outcomes in metastatic CRC patients with non-liver metastases (NLM) compared to those with liver metastases (LM) across different lines of treatment. MethodsA total of 17,924 mCRC patients included in 26 trials from the ARCAD CRC database were analyzed. The analysis was conducted based on the presence or absence of LM across different treatment groups: chemotherapy (CT) alone, CT + anti-VEGF, CT + anti-EGFR in KRAS wild-type tumors, within the first-line (1 L) and second-line (2 L), and patients enrolled in third-line (≥3 L) trials treated with trifluridine/tipiracil or regorafenib or placebo. The endpoints were overall survival (OS), progression-free survival (PFS), and overall response rate (ORR). ResultsOut of the 17,924 patients, 14,066 had LM (30.6 % with only liver involvement and 69.4 % with liver and other metastatic sites), while 3858 patients had NLM. In the CT alone and CT + anti-VEGF subgroups, NLM patients showed better OS and PFS in the 1 L and 2 L settings. However, in the CT + anti-EGFR 1 L and 2 L subgroups, there was no significant difference in OS and PFS between NLM and LM patients. In the ≥ 3 L subgroups, better OS and PFS were observed in NLM patients. ORRs were higher in LM patients than in NLM patients across all cohorts treated in the 1 L and only in the anti-EGFR cohort in the 2 L. ConclusionLM is a poor prognostic factor for mCRC increasing from 1 L to ≥ 3 L except for patients in 1 L and 2 L receiving CT+anti-EGFR. These data justify using LM as a stratification factor in future trials for patients with unresectable mCRC.

Sacituzumab govitecan (SG) vs docetaxel (doc) in patients (pts) with metastatic non-small cell lung cancer (mNSCLC) previously treated with platinum (PT)-based chemotherapy (chemo) and PD(L)-1inhibitors (IO): Primary results from the phase 3 EVOKE-01 study.

LBA8500 Background: In pts with mNSCLC who progress on PT-based chemo and IO, doc is standard of care, but outcomes remain poor. SG, a Trop-2-directed antibody drug conjugate, showed durable response and tolerable safety in pretreated mNSCLC. We report results from the phase 3, randomized, open-label EVOKE-01 study comparing SG vs doc. Methods: Pts with mNSCLC with disease progression after PT-based chemo and IO were randomized 1:1 (stratified by histology, best response to last prior IO, and prior treatment for actionable genomic alterations [yes/no]) to receive SG (10 mg/kg IV, days 1 and 8) or doc (75 mg/m2 IV, day 1) in 21-day cycles until progression or unacceptable toxicity. The primary endpoint was overall survival (OS); key secondary endpoints were investigator assessed progression-free survival (PFS) and objective response rate (ORR), patient-reported outcomes (PROs), and safety. Results: As of Nov 29, 2023, 603 pts were randomized. Median (range) age was 65 (31–84) yrs; 55% had 1 prior therapy line. The study was not statistically significant for OS. A numerical improvement in OS, favoring SG, was seen (HR 0.84 [95% CI, 0.68–1.04; 1-sided P = 0.0534]) including in pts with squamous and nonsquamous histology. PFS and ORR are shown in the Table. A clinically meaningful difference in median OS favoring SG (3.5 mo) was seen in pts without response to last prior IO. PROs were improved with SG vs doc. Grade ≥3 treatment-emergent adverse event (TEAE) incidence was 66.6% (SG) and 75.7% (doc). Treatment-related AEs led to discontinuation in 6.8% (SG) and 14.2% (doc). Conclusions: Although statistical significance was not met, SG showed numerical improvement in OS vs doc. Results were consistent across all major subgroups including histology. Clinically meaningful improvement in OS was noted in pts without response to prior IO. SG was better tolerated than doc; observed safety was consistent with the known profile. Clinical trial information: NCT05089734 . [Table: see text]

Real-world data on the efficacy and safety of trastuzumab emtansine in patients with metastatic breast cancer previously treated with pertuzumab: Turkish oncology group multicenter study

We aimed to evaluate the efficacy and safety of trastuzumab emtansine in patients with metastatic breast cancer previously treated with pertuzumab plus trastuzumab and taxane. We reviewed the medical records of patients who were diagnosed with Human Epidermal Growth Factor Receptor 2 (HER-2) positive metastatic breast cancer and received pertuzumab and then TDM-1 between January 2014 and January 2021 from twenty- five cancer centers. The Kaplan- Meier method estimated progression-free survival (PFS) and overall survival (OS). Additionally, objective response rate (ORR), clinical benefit rate (CBR), and safety were evaluated. One hundred fifty-three patients were included,79.1% of the patients received TDM-1 in the second line, 90.8% had visceral metastasis, and 30.7% had central nervous system involvement. The PFS and OS of TDM-1 were evaluated according to the number of previous lines (on the 2nd line or more than two lines) metastatic sites (visceral and non-visceral) and the presence of central nervous metastasis. In TDM-1 therapy, PFS in second line therapy was ten months (95% CI: 7.7 − 12.2); this was statistically higher than later-line PFS, which was six months (95% CI: 3.3 to 8.6) (p = 0.004). The median OS time was 25 months (95% CI: 21.0 to 28.9) in patients treated with TDM-1 in the second line and 19 months (95% CI: 12.3 to 25.6) in patients who received later than the second line(p = 0.175). There were no significant differences in PFS time of patients with and without visceral and central nervous metastases. Our study showed that TDM-1 was also effective in patients using pertuzumab, contributes significantly to PFS when used in the second line compared to its use in the later line, and does not make any difference in OS.

Efficacy and safety of PD-1 inhibitors plus chemotherapy with or without endostatin for stage IV lung squamous cancer: a retrospective study.

The study aimed to analyze the efficacy and safety of PD-1 inhibitors plus chemotherapy with or without endostatin for stage IV lung squamous cell carcinoma (LUSC). A total of 219 patients with stage IV LUSC were included. 120 received PD-1 inhibitors plus chemotherapy with or without endostatin (IC ± A), of which 39 received endostatin (IC+A) and 81 did not receive endostatin (IC-A). 99 received chemotherapy with or without endostatin (C ± A). Endpoints included overall survival (OS), progression-free survival (PFS), adverse events (AEs), and immune-related adverse events (irAEs). The median PFS in the IC ± A group versus the C ± A group was 8 and 4 months (P < 0.001), and the median OS was 17 and 9 months (P < 0.001). There was no significant difference in any grade AEs between the IC ± A and C ± A groups (P > 0.05). The median PFS in the IC+A group versus the IC-A group was 11 and 7 months (P = 0.024), and the median OS was 34 and 15 months (P = 0.01). There was no significant difference between the IC+A group and the IC-A group for all grade AEs and irAEs (P > 0.05). The subgroup analysis showed that patients with LIPI = 0 had significant OS and PFS benefits in IC+A group, while for patients with LIPI = 1-2, there was no significant difference in OS and PFS benefits between the IC+A group and IC-A group. PD-1 inhibitors plus chemotherapy with endostatin might be first-line treatment for patients with stage IV LUSC.

Comparative Validity of the ALBI Grade and CTP Score in Predicting Overall Survival in Patients Receiving TACE Plus Sorafenib Therapy for Hepatocellular Carcinoma

Background: Hepatocellular carcinoma (HCC) significantly impacts global health, with liver function being a critical factor in patient prognosis. The ALBI grade and Child-Turcotte Pugh (CTP) score are both used to evaluate liver function in HCC patients, but their effectiveness in predicting survival outcomes varies. Objective: This study aimed to evaluate and compare the effectiveness of the ALBI grade and CTP score in predicting overall survival (OS) in HCC patients undergoing combined therapy with sorafenib and transarterial chemoembolization (TACE). Methods: Conducted at Jinnah Hospital Lahore and Hijaz Hospital between January 2019 and June 2023, this study included 103 HCC patients with CTP scores of 5 and 6. We analyzed the predictive values of the ALBI grade and CTP score for OS using multivariate analyses and time-dependent ROC curves. Results: Multivariate analysis indicated significant differences in OS among patients categorized by both scoring systems, with hazard ratios of 2.16 (P&lt;0.001) for the CTP score and 1.49 (P=0.035) for the ALBI grade. Time-dependent ROC analysis showed that the ALBI grade was more effective in discriminating long-term survival. It also remained a significant predictor of OS in a larger number of patient subgroups compared to the CTP score. Conclusion: The ALBI grade demonstrates superior prognostic stratification compared to the CTP score in HCC patients treated with TACE and sorafenib who have stable liver function.

Developing a prognostic model using machine learning for disulfidptosis related lncRNA in lung adenocarcinoma

Disulfidptosis represents a novel cell death mechanism triggered by disulfide stress, with potential implications for advancements in cancer treatments. Although emerging evidence highlights the critical regulatory roles of long non-coding RNAs (lncRNAs) in the pathobiology of lung adenocarcinoma (LUAD), research into lncRNAs specifically associated with disulfidptosis in LUAD, termed disulfidptosis-related lncRNAs (DRLs), remains insufficiently explored. Using The Cancer Genome Atlas (TCGA)-LUAD dataset, we implemented ten machine learning techniques, resulting in 101 distinct model configurations. To assess the predictive accuracy of our model, we employed both the concordance index (C-index) and receiver operating characteristic (ROC) curve analyses. For a deeper understanding of the underlying biological pathways, we referred to the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) for functional enrichment analysis. Moreover, we explored differences in the tumor microenvironment between high-risk and low-risk patient cohorts. Additionally, we thoroughly assessed the prognostic value of the DRLs signatures in predicting treatment outcomes. The Kaplan–Meier (KM) survival analysis demonstrated a significant difference in overall survival (OS) between the high-risk and low-risk cohorts (p < 0.001). The prognostic model showed robust performance, with an area under the ROC curve exceeding 0.75 at one year and maintaining a value above 0.72 in the two and three-year follow-ups. Further research identified variations in tumor mutational burden (TMB) and differential responses to immunotherapies and chemotherapies. Our validation, using three GEO datasets (GSE31210, GSE30219, and GSE50081), revealed that the C-index exceeded 0.67 for GSE31210 and GSE30219. Significant differences in disease-free survival (DFS) and OS were observed across all validation cohorts among different risk groups. The prognostic model offers potential as a molecular biomarker for LUAD prognosis.

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.

Age-related nomogram revealed optimal therapeutic option for older patients with primary liver cancer: less is more.

Age bias in therapeutic decisions for older patients with cancer exists. There is a clear need to individualize such decisions. Based on the Surveillance, Epidemiology and End Results (SEER) database, 5081 primary liver cancer (PLC) patients between 2010 and 2014 were identified and divided into <64, 64-74 and >74 years group. Each group was randomly divided into training and internal validation cohorts, and patients who were diagnosed between 2015 and 2016 were included as an external validation. The nomogram model predicting overall survival (OS) was generated and evaluated based on the Cox regression for the influencing factors in prognosis. The K-M analysis was used to compare the difference among different treatments. KM analysis showed a significant difference for OS in three age groups (P < 0.001). At the same time, we also found different prognostic factors and their importance in different age groups. Therefore, we created three nomograms based on the results of Cox regression results for each age group. The c-index was 0.802, 0.766, 0.781 respectively. The calibration curve and ROC curve show that our model has a good predictive efficacy and the reliability was also confirmed in the internal and external validation set. An available online page was established to simplify and visualize our model (http://124.222.247.135/). The results of treatment analysis revealed that the optimal therapeutic option for PLCs was surgery alone. The optimal therapeutic option for older PLCs was surgery alone. The generated dynamic nomogram in this study may be a useful tool for personalized clinical decisions.

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.

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

The VERIFY study aimed to determine the efficacy of vandetanib in patients with differentiated thyroid cancer (DTC) that is either locally advanced or metastatic and refractory to radioiodine (RAI) therapy. Specifically, VERIFY is a randomized, double-blind, multicenter phase III trial aimed to determine the efficacy and safety of vandetanib in tyrosine kinase inhibitor-naive patients with locally advanced or metastatic RAI-refractory DTC 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 a placebo. Median PFS was 10.0 months in the vandetanib group and 5.7 months in the placebo group (hazard ratio: 0.75; 95% CI: 0.55-1.03; P = 0.080). OS was not significantly different between treatment arms. Common Terminology Criteria for Adverse Events (CTCAE) 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.

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.

Interaction of BRCA1 vs BRCA2 pathogenic variants with primary tumor location in pancreatic cancer.

e16326 Background: BRCA1/2 germline or somatic pathogenic variants (PVs) are found in 5-10% of pancreatic adenocarcinoma (PDAC) patients. Recent data suggest that BRCA2 PVs may be associated with increased overall survival (OS) compared to BRCA1 PVs after adjusting for treatment and clinical characteristics. Additionally, pancreatic tail PDAC was found to harbor PVs in BRCA1/2 more frequently compared to PDAC within the pancreatic head (HOP). We hypothesized that tumor location in patients with BRCA1 and BRCA2 PVs would associate with overall survival and somatic mutation profile. Methods: We conducted a retrospective cohort study using a database of patients with PDAC and BRCA1/2 PVs at an academic center. Demographic and clinical data were compared by Fisher’s exact test. OS was measured using date of death or last follow-up and compared by Cox proportional hazards regression adjusting for treatment with platinum-based chemotherapy and curative-intent surgical resection. Cases with available next generation somatic sequencing were reviewed. Results: There were no significant differences in age, sex, stage at diagnosis, ECOG status at diagnosis, tumor location, treatments, or sites of metastasis between patients with BRCA1 vs BRCA2 PVs. In the overall cohort, we observed no significant difference in OS between patients with BRCA1 vs BRCA2 (17.0 vs 20.2 months). However, survival analysis stratified by tumor location demonstrated that BRCA1 patients with HOP tumors had significantly worse OS compared to BRCA2 patients with HOP tumors (13.1 vs 25.7 months, p = 0.014) and had a significantly higher rate of TP53 mutations (100% vs 50%, p = 0.032). No significant differences in OS or rates of TP53 mutations were observed in the body/tail of the pancreas. Conclusions: These results suggest that there may be differences in rates of somatic variants between BRCA1- and BRCA2-related HOP PDAC and suggest an interaction between BRCA1/2 tumor biology and anatomical location. [Table: see text]

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.