Disease-free Survival Outcomes Research Articles

The Effect of Thyrotropin Suppression on Survival Outcomes in Patients with Differentiated Thyroid Cancer: A Systematic Review and Meta-Analysis.

Background: Long-term management of intermediate- and high-risk differentiated thyroid cancer (DTC) involves thyrotropin (TSH) suppression with thyroid hormone to prevent potential stimulation of TSH receptors on DTC cells, leading to tumor growth. However, the current guidelines recommending TSH suppression are based on low- to moderate-quality evidence. Methods: We performed a systematic review and meta-analysis of studies evaluating the role of TSH suppression in intermediate- and high-risk DTC patients (≥18 years) treated as per regional guideline-based therapy with a follow-up duration of 5 years (PROSPERO #252396). TSH suppression was defined as "below normal reference range" or, when known, <0.5 mIU/L. Primary outcome measures included (i) composite of progression-free survival (PFS), disease-free survival (DFS), and relapse-free survival (RLFS), and (ii) composite of disease-specific survival (DSS), and overall survival (OS). Secondary outcome included a composite of cardiac or skeletal adverse events. All outcomes and comparisons were represented as TSH suppression versus TSH nonsuppression. Randomized controlled trials, cohort studies, and case-control studies were included for analysis. Pooled hazard ratio (HR) and 95% confidence interval (CI) were calculated using random-effects model. Results: Abstract screening was performed on 6,369 studies. After the exclusion of irrelevant studies and full-text screening, nine studies were selected for the final meta-analysis. Based on seven studies (3,591 patients), the composite outcome of PFS, DFS, and RLFS was not significantly different between TSH suppression and nonsuppression groups (HR: 0.75; 95% CI: 0.48-1.17; I2 = 76%). Similarly, a DSS and OS composite outcome assessment based on four studies (3,616 patients) did not favor TSH suppression (HR: 0.69; 95% CI: 0.31-1.52; I2 = 88%). Even after excluding studies of lower quality, the primary outcomes were not significantly different between the TSH suppression and nonsuppression cohorts. The secondary outcome, obtained from two studies (1,294 patients), was significantly higher in the TSH-suppressed groups (HR: 1.82; 95% CI: 1.30-2.55; I2 = 0%). Significant study heterogeneity was noted for primary outcomes. Conclusion: TSH suppression in intermediate- and high-risk DTC may not improve survival outcomes but may increase the risk of secondary complications. However, the limited evidence and study heterogeneity warrant cautious interpretation of our findings. Registration: PROSPERO #252396.

Real-world efficacy of adjuvant therapy for totally resected stage I lung adenocarcinoma patients with pathological high-risk factors: propensity score analysis

BackgroundWe investigated the real-world efficacy of adjuvant therapy for stage I lung adenocarcinoma patients with pathological high-risk factors.MethodsStudy participants were enrolled from November 1, 2016 and December 31, 2020. Clinical bias was balanced by propensity score matching. Disease-free survival (DFS) outcomes were compared by Kaplan–Meier analysis. The Cox proportional hazards regression was used to identify survival-associated factors. p ≤ 0.05 was the threshold for statistical significance.ResultsA total of 454 patients, among whom 134 (29.5%) underwent adjuvant therapy, were enrolled in this study. One hundred and eighteen of the patients who underwent adjuvant therapy were well matched with non-treatment patients. Prognostic outcomes of the treatment group were significantly better than those of the non-treatment group, as revealed by Kaplan-Meier analysis after PSM. Differences in prevention of recurrence or metastasis between the targeted therapy and chemotherapy groups were insignificant. Adjuvant therapy was found to be positive prognostic factors, tumor size and solid growth patterns were negative.ConclusionsAdjuvant therapy significantly improved the DFS for stage I lung adenocarcinoma patients with high-risk factors. Larger prospective clinical trials should be performed to verify our findings.

Short- and long-term outcome differences between patients undergoing left and right colon cancer surgery: cohort study

PurposeSince the literature currently provides controversial data on the postoperative outcomes following right and left hemicolectomies, we carried out this study to examine the short- and long-term treatment outcomes.MethodsThis study included consecutive patients who underwent right or left-sided colonic resections from year 2014 to 2018 and then they were followed up. The short-term outcomes such as postoperative morbidity and mortality according to Clavien-Dindo score, duration of hospital stay, and 90-day readmission rate were evaluated as well as long-term outcomes of overall survival and disease-free survival. Multivariable Cox regression analysis was performed of overall and progression-free survival.ResultsIn total, 1107 patients with colon tumors were included in the study, 525 patients with right-sided tumors (RCC) and 582 cases with tumors in the left part of the colon (LCC). RCC group patients were older (P < 0.001), with a higher ASA score (P < 0.001), and with more cardiovascular comorbidities (P < 0.001). No differences were observed between groups in terms of postoperative outcomes such as morbidity and mortality, except 90-day readmission which was more frequent in the RCC group. Upon histopathological analysis, the RCC group’s patients had more removed lymph nodes (29 ± 14 vs 20 ± 11, P = 0.001) and more locally progressed (pT3-4) tumors (85.4% versus 73.4%, P = 0.001). Significantly greater 5-year overall survival and disease-free survival (P = 0.001) were observed for patients in the LCC group, according to univariate Kaplan-Meier analysis.ConclusionsPatients with right-sided colon cancer were older and had more advanced disease. Short-term surgical outcomes were similar, but patients in the LCC group resulted in better long-term outcomes.

Predicting factors and clinical outcome of biochemical incomplete response in middle eastern differentiated thyroid carcinoma.

The aim of this study was evaluate biochemical incomplete response (BIR) in Middle Eastern differentiated thyroid cancer (DTC), identify factors that could predict BIR before radioactive iodine (RAI) ablation and to investigate the long-term clinical outcome of DTC patient exhibiting BIR to initial therapy. We retrospectively evaluated 1286 DTCs from Middle Eastern ethnicity who underwent total thyroidectomy and RAI therapy. Demograpic and clinico-pathological factors predicting BIR were evaluated. The outcome of these patients was analyzed using primary outcome of structural disease and disease-free survival (DFS). With a median follow-up of 10 years, 266 (20.7%) patients had BIR. High pre-ablation stimulated thyroglobulin (presTg), presence of lymph node metastasis, male gender and delayed initial RAI therapy (≥3 months) after thyroidectomy were significant independent predictors of BIR. Upon evaluating long-term clinical outcomes in 266 patients with BIR, we found 36.8% of patients developed structural disease. Male sex (OR = 1.56; 95% CI = 1.05-2.30; p = 0.0272) and increasing Tg after initial therapy (OR = 4.25; 95% CI = 1.93-10.82; p = 0.0001) were independent risk factors for structural disease in patients with BIR. DFS was significantly worse if both these risk factors existed concomitantly (p < 0.0001). To achieve the fair efficacy of RAI therapy, early prediction of BIR before RAI ablation is desirable. Our finding of the clinico-pathological factors (high presTg level, LNM, delayed RAI therapy and male gender) could serve as easy and robust early predictors of BIR. In addition, DTC patients exhibiting BIR had a high risk of structural disease and hence personalized management approach would be preferable for BIR patients to ensure best clinical outcome.

Abstract PO2-06-14: Kynurenine induces senescence reprogramming to promote metastasis in young triple-negative breast cancer

Abstract Triple-negative breast cancer (TNBC), which has been associated with a high risk of relapse and poor prognosis, has an increasing incidence among young women and ongoing inferior long-term outcomes. Given TNBC arising at a young age are more likely to present at advanced stages and to have aggressive biology, it is necessary to investigate the underlying mechanism and develop multidisciplinary strategies for optimal therapy of young women with breast cancer. Here, we integrated the multiomics data of our large TNBC cohort (n=456) to investigate different molecular mechanism between younger and older patients in the context of genetic and transcriptional subtypes and immune cell infiltration. We discovered that young TNBC patients exhibited a poorer outcome of both 2-year relapse-free survival and 2-year distant disease-free survival. Multi-omics analysis revealed that kynurenine (KYN) was preferentially enriched in young TNBC and activated tumor cellular senescence pathway which was positively correlated with increased metastasis. Mechanistically, KYN activated the aryl hydrocarbon receptor (AHR) signaling pathway in an ARNT2-dependent manner which was critical for cellular senescence, to mediate senescence reprogramming and promote tumor metastasis in young TNBC. Our findings unveil a novel interplay between cancer cell metabolites and cell senescence, which provides valuable insights that can potentially enhance therapeutic strategies for young TNBC patients. Keywords: young TNBC, metastasis, kynurenine, cellular senescence, AHR pathway Citation Format: Cui-Cui Liu, Ke-da Yu. Kynurenine induces senescence reprogramming to promote metastasis in young triple-negative breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-06-14.

Abstract PO2-09-08: Biological and non-biological predictors of breast cancer disease-free survival among young Black females

Abstract Introduction: Young Black females bear a disproportionate burden of breast cancer (BC) deaths compared to White females yet remain underrepresented in clinical studies. We sought to discover predictors of disease-free survival (DFS) in a cohort of young Black females with BC. Methods: Black females diagnosed with invasive BC ≤ age 50 from 2005 to 2016 were recruited through the Florida and Tennessee state cancer registries. Participants were asked to complete a questionnaire, medical records release, and tissue/tumor release. Saliva was also requested for germline DNA extraction. For the primary outcome of BC DFS, univariate analyses were conducted using the following variables: proportion of West African ancestry, RNA expression based on PAM50 analyses, body mass index (BMI), social determinants of health (i.e., employment and insurance), immunohistochemistry (IHC) subtype, treatment category (i.e., chemotherapy, radiation, and surgery), and BC family history. Multivariate analyses were conducted using backward selection among these variables to analyze in the reduced model. Results: Of 701 consented, 687 participants with early-stage disease were included in the analysis; 14 participants with stage 4 disease at diagnosis were excluded. Among the 687 participants, the median age at diagnosis was 44, 28% had triple-negative breast cancer (TNBC), 13% were deceased, and 5% had recurrent disease. Clinically, participants with TNBC and lymph node involvement had worse BC DFS (p=0.001 and p=0.0002, respectively). Socio-economically, full-time employement was associated with higher BC DFS (p=0.0003). Among those for whom global ancestry data were available (n=551), multivariate analysis showed an association between increased percent of West African ancestry and worse BC DFS with HRIQR=1.23*, which approached significance (p=0.085). Additional subgroup analyses among those with hormone receptor-positive (HR+) (estrogen and/or progesterone receptor positive) BC (n=431) showed that participants with private insurance had better BC DFS (HR=0.45; p=0.05), while those with lymph node involvement had worse BC DFS (HR=2.07; p=0.001). Among HR+ participants with available ancestry data (n=349), worse BC DFS was associated with increased West African ancestry (p=0.05) and lymph node involvement (p=0.08). When ancestry was included in the model, private insurance was no longer associated with BC DFS in this HR+ subgroup (p=0.31). Other predictors analyzed did not reach statistical significance. Conclusion: Our findings confirm prior established adverse predictors of BC DFS, such as TNBC with lymph node involvement and the protective effect of full-time employment. We also found a novel association with West African ancestry among patients with HR+ breast cancer. Although further large-scale studies are needed, results from this cohort of young Black females with BC and highlight the critical need to support research to understand biological and non-biological factors contributing to BC DFS and develop targeted strategies to improve survival outcomes. * HRIQR is the ratio of hazard rates corresponding to upper and lower quartiles of percent West African (interquartile range (IQR): 70.0%-80.8%). Citation Format: Sonya Reid, Run Fan, Lindsay Venton, Anne Weidner, Ann Tezak, Mya Roberson, Susan Vadaparampil, Xuefeng Wang, Sean Yoder, Marilin Rosa, Jibril Hirbo, Jennifer Whisenant, Jennifer Pietenpol, Sheila Rajagopal, Brian Lehmann, Fei Ye, Tuya Pal. Biological and non-biological predictors of breast cancer disease-free survival among young Black females [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-09-08.

Abstract PO1-19-05: COGNITION/-GUIDE – Implementation of Precision Oncology in Early High-Risk Breast Cancer

Abstract Background: The concept of precision oncology is nowadays increasingly implemented into clinical practice but is predominantly restricted to the metastatic setting limiting the benefits to prolongation of progression-free-survival (PFS). Implementation of precision oncology at an earlier disease stage with less tumor burden, heterogeneity and a higher capacity of tumor lesions to inform on the molecular tumor landscape holds the promise to impact cure rates. Methods: The prospective COGNITION/-GUIDE precision oncology platform encompasses the COGNITION diagnostic multi-omics biomarker screening platform (NCT05906407) linked to the multi-arm phase II COGNITION-GUIDE umbrella trial (NCT05332561). Based on a two-step consenting procedure, patients with early breast cancer (eBC) and poor response towards standard-of-care (SOC) neoadjuvant chemotherapy (NACT) are first enrolled into the COGNITION diagnostic platform. Residual bulk tumors are subjected to whole-genome- (WGS)/whole exome- (WES) and RNA-sequencing to enable streamlined detection of a rigorous biomarker-framework for subsequent genomics-guided arm allocation. Pilot analyses revealed that 78% (81/104) of high-risk tumors (TNBC or HER2+ BC with non-pCR or HR+/HER2- BC with non-pCR and CPS-EG score ≥ 3, or ypN+ and CPS-EG score ≥ 2) can be successfully sequenced and discussed within an interdisciplinary molecular tumor board. In 67% (70/104) eligible biomarker-profiles could be identified for potential biomarker-guided therapeutic intervention. In a second step, having completed all standard-of-care neoadjuvant and post-neoadjuvant treatments (except endocrine therapy, which can be administered simultaneously to the experimental therapy), patients can be enrolled into one of 6 biomarker-based arms in the COGNITION-GUIDE phase II trial (atezolizumab, inavolisib, ipatasertib, olaparib, sacituzumab govitecan or trastuzumab/pertuzumab). Primary end point is invasive disease-free survival (IDFS) at 4 years after surgery in the whole study population. Secondary endpoints are overall survival (OS), IDFS in each treatment arm, distant disease-free survival (DDFS) and patient-reported outcomes (PROs). Enrollment in COGNITION-GUIDE started in Q2/2023 and 240 patients will be enrolled in 5 German sites until Q2/2027. A comprehensive biomarker discovery program is integrated on longitudinal tumor tissue and liquid biopsies for exploratory analyses. Further clinical work and accrual will be reported at the meeting. Conclusion: The theranostic COGNITION/-GUIDE platform moves the concept of precision oncology to a potentially curative but still high-risk stage of eBC following SOC NACT. Hence, this novel application in the field of precision oncology harbours the prospect to increase cure rates. Citation Format: Verena Thewes, Luise Strassl, Marc Zapatka, Mario Hlevnjak, Constantin Pixberg, Christian Maurer, Katharina Smetanay, Carlo Fremd, Laura Michel, Sabine Heublein, Celina V. Wagner, Jan-Philip Suppelna, Lars Buschhorn, Albrecht Stenzinger, Renate Haidinger, Eva Schumacher-Wulf, Sibylle Loibl, Pauline Wimberger, Jens-Uwe Blohmer, Peter A. Fasching, Wolfgang Janni, Richard F. Schlenk, Peter Lichter, Andreas Schneeweiss. COGNITION/-GUIDE – Implementation of Precision Oncology in Early High-Risk Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-19-05.

Abstract PO3-17-01: Brazilian Real-world data of HR+ HER2- early-stage Breast Cancer (BC) patients are poor when compared to control arms of recent adjuvant clinical trials

Abstract INTRODUCTION: In Brazil, BC is the most common neoplasm among women, with 73k new cases annually. Adjuvant hormone therapy (HT) options are evolving with personalized strategies based on risk stratification. Real-world data (RWD) plays a crucial role in understanding the outcomes in BC patients (pts) in low- and middle-income countries, where significant health disparities, access gaps, and barriers to the implementation of guidelines exist. This study aims to assess the epidemiologic profile, practice patterns, and real-world outcomes of pts with ER+ HER2- stage I-III BC treated in the largest network of private oncology services in Brazil and compare results with control arms of recent clinical trials evaluating CDK4/6 inhibitors in adjuvant setting. METHODS: Retrospective RWD study from Oncoclínicas Group with longitudinal EHR data from 2017 to 2022 merged in a platform where structured variables (demographics, tumor staging, pharmacy records) are integrated with unstructured data from physician notes and digitized pathology-molecular reports using technology-based abstraction performed by expert human curators that follow mCODE standards and predefined ontology. Treatment patterns and invasive disease-free survival (IDFS) outcomes were collected. Regarding risk stratification, pts were classified as high-risk (HR) if: (i) 4+ axillary lymph nodes (LN), or (ii) 1-3 LN and grade 3 and/or Ki620% and/or high-risk ODX/Mammaprint; intermediate-risk (IR) if: (iii) 1-3 LN with grade 1-2 and/or Ki67 &amp;lt; 20% and/or non-high-risk ODX/Mammaprint, or (iv) N0 with grade 2-3 and/or Ki67 &amp;gt;20% and/or high-risk ODX/Mammaprint; and low-risk (LR) if: (v) all other stages I and IIA not having the risk factors above. RESULTS: From over 30k BC pts in Oncoclínicas Database, 19k had HR+/HER2- early BC, 12k were treated in high-volume clinics, and 1,786 cases were selected for the study (diagnosis and first treatment in the last 6 years, complete histopathology and pharmacy registries). The median age was 57 years (27-96), 566 (32%) pts were premenopausal, 1052 (59%) had stage I disease, 372 (21%) stage IIA, 165 (9%) stage IIB and 197 (11%) stage III BC. Regarding risk stratification, 1,179 (66%) were LR, 351 (20%) IR, and 256 (14%) HR. In post-menopausal pts, aromatase inhibitor (AI) was used by 74% of pts with LR, 79% with IR and 83% with HR. In premenopausal pts, ovarian function suppression (OFS) – combined with tamoxifen or AI – was prescribed to 18% of LR pts, 15% of IR pts, and 48% of HR pts. Chemotherapy (CT) was offered to 32%, 38%, and 73% of postmenopausal pts in LR, IR, and HR groups. In premenopausal pts, 55%, 57%, and 78% received CT in LR, IR, and HR groups. The 3-year iDFS in the general population was 85%, reaching 80% in premenopausal and 86% in postmenopausal pts. The overall 3y iDFS was 87% in the LR, 86% in IR, and 72% in HR. Among premenopausal pts, the 3y iDFS was 81% in LR, 92% in IR, and 64% in the HR group. While the risk distribution of our cohort is similar to recent clinical trials, the 3y iDFS outcomes were numerically lower to those observed in the control groups of the pivotal trials evaluating adjuvant CDK4/6 inhibitors. In the HR group, the 3y iDFS was 72% (versus 84% 3y iDFS in the control arm of the MonarchE trial). Combining the IR/HR groups, the 3y iDFS was 80% (versus 87% in the control arm of NATALEE trial). CONCLUSION: In this large RWD cohort treated in a private setting in Brazil, most pts are diagnosed with stage I and LR BC. In this cohort, a significant proportion of premenopausal pts with IR/HR are not treated with OFS and do not receive CT. Real-world survival outcomes of Brazilian women with HR+ HER2- early BC treated in private clinic are inferior to those observed in recent clinical trials, especially in the premenopausal pts. In public healthcare system, where prevalence of HR disease is higher and access to essential treatments more limited, outcomes might even be worsened compared to the ones presented here. Citation Format: Aline Goncalves, Tomas Reinert, Max S. Mano, Heloisa Cruz, Cristiano Resende, Gustavo Bretas, Carlos Barrios, Matheus Costa e Silva, Rafael Paes, Guilherme Silva, Erika Martins, Fernanda Koyama, Bruno Ferrari, Carlos Gil Ferreira, Pedro Aguiar Junior, Rodrigo Dienstmann. Brazilian Real-world data of HR+ HER2- early-stage Breast Cancer (BC) patients are poor when compared to control arms of recent adjuvant clinical trials [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-17-01.

Abstract PO3-29-05: Clinical risk score to predict overall survival and breast cancer recurrence in phase 3 TAILORx trial and the Surveillance, Epidemiology, and End Results (SEER) Database populations

Abstract Background: Overall survival (OS) is the gold standard and most relevant endpoint in oncology research and patient care. It underscores a need to develop methods to estimate the likelihood of mortality in breast cancer. Methods: We evaluated molecular and clinical measures that predicted mortality risk using multiple logistic regression and developed a clinical risk score (CS) in 8,905 patients from the phase 3 TAILORx trial. Association of CS with mortality in patients at low, intermediate, and high risks was analyzed by Kaplan-Meier and multivariable Cox proportional-hazards regression analyses. The score was validated in an independent population of 148,301 patients with node-negative, hormone-receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer in the SEER database. Likelihood ratio (LR) test and c-index were used to compare prognostic information provided by CS and a 21-gene recurrence score (RS) to OS, invasive disease-free survival (DFS), recurrence-free interval (RFI), and distant recurrence-free interval (dRFI). Results: The 10-year mortality rates in low-risk, intermediate risk, and high-risk groups were 3.9% (95% CI 3.1 to 4.8), 37.2% (95% CI 23.4 to 51.1), and 75.8% (95% CI 54.1 to 97.4), respectively (P&amp;lt; 0.0001). Compared with low-risk score, intermediate (adjusted HR 45.5, 95% CI 32.2 to 64.9) and high-risk scores (HR 2026, 95% CI 1194 to 3483) were associated with risk of mortality, independent of demographics, tumor grade, RS, tumor size, PR, and treatment factors. The algorithm also predicted DFS, dRFI, and RFI outcomes (P&amp;lt; 0.0001 each), outperforming RS by both LR test and c-index estimate. Its validity was corroborated in the SEER population (intermediate risk: HR 9.3, 95% CI 6.7 to 13.3 and high-risk: HR 125.9, 95% CI 85.2 to 189.6). Conclusions: Clinical risk score robustly predicts risk of mortality in early-stage breast cancer populations. It provides more prognostic information than RS to survival and breast cancer recurrences. Citation Format: Sherry Yang, John Yu, Ninet Sinaii. Clinical risk score to predict overall survival and breast cancer recurrence in phase 3 TAILORx trial and the Surveillance, Epidemiology, and End Results (SEER) Database populations [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-29-05.

A Phase II Study of Neoadjuvant Chemoradiotherapy with Docetaxel, Cisplatin and 5-FU Followed by Surgical Resection in the Treatment of Locally Advanced Esophagogastric Junction Cancer and Locally Advanced Esophageal Cancer.

We conducted a phase II study evaluating chemoradiotherapy in patients with advanced esophageal cancer, using the docetaxel, cisplatin, and 5-fluorouracil (DCF) regimen followed by surgery. The primary purposes of this clinical trial were to assess the efficacy and safety of chemoradiotherapy employing the DCF regimen in the treatment of advanced esophageal cancer. We enrolled a total of 24 newly diagnosed esophageal cancer patients between April 2015 and November 2017 in this prospective study. The radiotherapy regimen consisted of a total dose of 45 Gy in 25 fractions. The chemotherapy protocol included docetaxel 35 mg/m2 for 1 h on day 1 and day 29, cisplatin 35 mg/m2 for 1 h on day 1 and day 29, and 5-FU 400 mg/m2 for 24 h on day 1-4 and day 29-32. The patients who accepted the re-staging exam should undergo surgery in 4-8 weeks after the completion of radiotherapy. The primary endpoints of this study were disease-free survival (DFS), overall survival (OS), and the evaluation of hematologic toxicity. The study population had a median age of 55.5 years, ranging from 44 to 66, with over 90% of the patients being male. The 5-year DFS was 37.1%, and the 5-year OS was 48.7%. The pathologic complete response rate was 45.8% (11/24). The most common types of toxicity were leukopenia and thrombocytopenia. No grade 3 or greater hematologic toxicity was reported. The use of the DCF regimen in neoadjuvant chemoradiotherapy followed by surgery demonstrated tolerable toxicity and achieved acceptable DFS and OS outcomes.

G-Protein Signaling Modulator 2 as a Potential Biomarker in Colorectal Cancer: Integrative Analysis Using Genetic Profiling and Pan-Cancer Studies.

Colorectal cancer (CRC) imposes a significant healthcare burden globally, prompting the quest for innovative biomarkers to enhance diagnostic and therapeutic strategies. This study investigates the G-protein signaling modulator (GPSM) family across several cancers and presents a comprehensive pan-cancer analysis of the GPSM2 gene across several gastrointestinal (GI) cancers. Leveraging bioinformatics methodologies, we investigated GPSM2 expression patterns, protein interactions, functional enrichments, prognostic implications, genetic alterations, and immune infiltration associations. Furthermore, the expression of the GPSM2 gene was analyzed using real-time analysis. Our findings reveal a consistent upregulation of GPSM2 expression in all GI cancer datasets analyzed, suggesting its potential as a universal biomarker in GI cancers. Functional enrichment analysis underscores the involvement of GPSM2 in vital pathways, indicating its role in tumor progression. The prognostic assessment indicates that elevated GPSM2 expression correlates with adverse overall and disease-free survival outcomes across multiple GI cancer types. Genetic alteration analysis highlights the prevalence of mutations, particularly missense mutations, in GPSM2. Furthermore, significant correlations between GPSM2 expression and immune cell infiltration are observed, suggesting its involvement in tumor immune evasion mechanisms. Collectively, our study underscores the multifaceted role of GPSM2 in GI cancers, particularly in CRC, emphasizing its potential as a promising biomarker for prognosis and therapeutic targeting. Further functional investigations are warranted to elucidate its clinical utility and therapeutic implications in CRC management.

Abstract 5151: High serum kidney injury marker-1 and high baseline tumor PD-L1 protein expression levels are independently associated with treatment effect in adjuvant nivolumab plus ipilimumab vs placebo in localized clear cell renal cell carcinoma

Abstract Introduction: CheckMate 914 (CM-914) Part A is a double-blind, phase III randomized trial of the Nivolumab (NIVO) plus Ipilimumab (IPI) vs placebo (PBO) in localized ccRCC. Our prior report from this study suggested a disease-free survival (DFS) benefit for NIVO+IPI among patients with Fuhrman grade 4, TNM stages PT2a and PT4, or sarcomatoid features, although the sample size was limited. It is known that high circulating KIM-1 is associated with worse DFS after nephrectomy. In this exploratory post hoc analysis, we investigated whether high KIM-1 may help identify a subset of patients who benefit from adjuvant NIVO+IPI. Methods: Patients (n=816) with RCC after nephrectomy were randomized in CM-914 Part A to receive NIVO+IPI or PBO as previously described. Assessment of KIM-1 levels was performed using enzyme linked immunoassay (ELISA) on pre-treatment (n=584) and matched on-treatment blood samples (n=584). We used pre-treatment tumor samples to assess PD-L1% tumor cell expression (%TC) in an PD-L1 IHC 28-8 pharm Dx assay. The association between biomarkers and DFS outcomes was investigated by Kaplan-Meier (KM) and Cox proportional hazards analysis. Results: Median baseline serum KIM-1 level was 102 (9.9 - 1055.7) pg/mL. Serum KIM-1 levels were higher in males vs females, ≥65 yrs vs &amp;lt;65 yrs, Asian vs white patients, and patients with partial vs radical nephrectomy. In the PBO arm, subjects with highest quartile of pre-treatment KIM-1 had significantly worse DFS than those from the three lower quartiles. In contrast, this DFS risk among the subjects within the highest KIM-1 quartile was mitigated with NIVO+IPI treatment. Among patients within the highest quartile of pre-treatment KIM-1, there was trend for better DFS for NIVO+IPI versus PBO, HR=0.6 (0.34-1.04). Increase in KIM-1 during study therapy was positively associated with higher DFS rate in both arms. Multivariable analysis showed that PD-L1 %TC was predictive at predefined PD-L1 cutoffs (&amp;gt;=1%, &amp;gt;=5%, and &amp;gt;=10%), associating with improved DFS compared to placebo. Subjects with high PD-L1 expression had a DFS benefit from NIVO+IPI independent of KIM-1. Conclusion: Circulating KIM-1 and tumor PD-L1 expression may enrich for benefit from IO therapy in adjuvant ccRCC and hence holds promise for informing risk stratification and patient inclusion in neoadjuvant or adjuvant clinical trials. Citation Format: Sai Vikram Vemula, Wenxin Xu, Yu Wang, Xiaowen Liu, Jorge Ruiz de Somocurcio, David McDermott, Jun Li, Rupal Bhatt, Chung-Wei Lee, Burcin Simsek, Saurabh Gupta, Robert Motzer. High serum kidney injury marker-1 and high baseline tumor PD-L1 protein expression levels are independently associated with treatment effect in adjuvant nivolumab plus ipilimumab vs placebo in localized clear cell renal cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5151.

Effect of Sarcopenia on the Prognosis of Clinical Outcomes in Patients With Hepatocellular Carcinoma After Hepatic Resection.

We aimed to study the prognostic impact of sarcopenia on overall survival (OS), disease-free survival (DFS), and postoperative outcomes among patients with Hepatocellular carcinoma (HCC) who underwent curative hepatic resection. Data were collected retrospectively from patients with HCC underwent curative hepatic resection and preoperative abdominal computed tomography (CT) at our institution between January 2010 and December 2020. Sarcopenia was evaluated by the skeletal muscle mass at the inferior direction of the third-lumbar-vertebra (L3) cross-sectional area based on preoperative CT imaging using software analysis. Cutoff values for skeletal muscle index (SMI) were 43.75 and 41.10cm2/m2 for males and females. The patients were classified into sarcopenia and nonsarcopenia groups. The association between preoperative sarcopenia and clinicopathological factors, impact of sarcopenia on survival, and postoperative outcomes were analyzed. Sarcopenia was present in 39 of 83 (47.0%) patients who underwent curative hepatic resection for HCC and was significantly correlated with lower SMI, lower serum albumin levels, higher intraoperative blood loss, higher postoperative complications, and longer hospital stay. The 5-year OS was significantly lower in sarcopenic patients than in nonsarcopenic patients (58.2% vs 83.6%; P = .006), but the 5-year DFS was not significantly different between the 2 groups. Multivariate analysis revealed that sarcopenia was a significant risk factor for poor OS (HR 4.728; 95% CI, 1.458-15.329; P = .010). Sarcopenia was identified as a prognostic factor for poor OS after hepatic resection, and major postoperative complications were more frequent in sarcopenia. Early sarcopenia detection and management may improve OS and clinical outcomes in postoperative HCC.

O105: Evaluating Surgical Approaches in Non-Small Cell Lung Cancer: Lobectomy vs Sublobar Resection

Abstract Background Lung Cancer remains the leading cause of cancer-related mortality, with non-small cell lung cancer (NSCLC) accounting for 85% of cases. Lobectomy has long been regarded as the gold-standard treatment for early-stage NSCLC. A shifting paradigm towards lung-sparing procedures such as sublobar resection, may benefit patients with limited respiratory reserve or high comorbidity index. This study aims to compare survival outcomes between patients undergoing lobectomy and sublobar resection. Methods This was a tertiary retrospective cohort study comparing disease-free survival (DFS), overall survival (OS) and postoperative outcomes in lobectomy and sublobar patients between 2013 and 2023 (n=3983). Propensity matched analysis was employed to adjust for treatment selection bias, calculated using a logistic regression model and incorporated eight covariates (n=528). Baseline, post-operative, and survival data were extracted from the hospital database. Comparison of baseline and post-operative characteristics involved Wilcoxon rank sum test, Fisher’s exact test and Pearson’s Chi-squared test. Kaplan Meier estimates and Multivariate Cox Regression were used to evaluate survival. p&amp;lt;0.05 was considered significant. Results No significant inter-cohort differences were observed in either DFS (log-rank p=0.32), OS (log-rank p=0.47), or 90-day mortality (log-rank p=0.78). Sublobar resection exhibited shorter post-operative length of stay (p&amp;lt;0.05). Conversely, both approaches demonstrated comparable resection margins and complication rates. Significant predictors of survival were age, gender and low Eastern Cooperative Oncology Group (ECOG) performance status (p&amp;lt;0.05). Conclusion These findings further support the non-inferiority of sublobar resection to lobectomy for stage 1 lung cancer. Additionally, improved perioperative outcomes may make sublobar resection more desirable for higher risk patients.

Total neoadjuvant therapy for locally advanced rectal cancer: a three-group propensity score matched study

PurposeTotal neoadjuvant therapy (TNT) has emerged as a therapeutic approach for locally advanced rectal cancer (LARC). However, the optimal chemotherapy cycles within TNT remain uncertain. This study aimed to evaluate and compare the prognostic efficacy of varying cycles of chemotherapy during TNT for LARC.MethodsPatients diagnosed with LARC (T3-4N0M0/T1-4N1-2M0), who underwent TNT or chemoradiotherapy followed by total mesorectal excision (TME) between 2015 and 2020, were retrospective included. Patients were categorized into three groups based on their neoadjuvant strategy: CRT (long-course chemoradiotherapy), STNT (long-course CRT with one to three cycles of chemotherapy), and LTNT (long-course CRT with four or more cycles of chemotherapy). Propensity score matching (PSM) based on gender, age, body mass index, tumor distance from the anal verge, clinical T stage, clinical N stage, and mesorectal fascia status was employed to reduce confounding bias. Primary endpoints were disease-free survival (DFS) and metastasis-free survival (MFS).ResultsThe study comprised 372 patients, with 73 patients in each group after PSM. Compared with CRT, both STNT and LTNT demonstrated improved DFS (5-year rate: 59.7% vs. 77.8% vs. 76.5%, p = 0.027) and MFS (5-year rate: 65.1% vs. 81.3% vs. 81.4%, p = 0.030). There was no difference in DFS or MFS between STNT and LTNT. These favorable outcomes were consistent among subgroups defined by tumor distance from the anal verge ≥ 5 cm, clinical T3 stage, clinical N positive status, or involved mesorectal fascia.ConclusionCompared to CRT, both STNT and LTNT demonstrated improved DFS and MFS outcomes. Notably, survival outcomes were similar between STNT and LTNT, suggesting that chemotherapy cycles in TNT may not significantly impact survival.

Current analysis of the survival implications for minimally invasive surgery in the treatment of early-stage cervix cancer.

Early-stage cervical cancer (ESCC) is managed with radical hysterectomy, a procedure that can be performed either via open surgery or minimally invasive surgery (MIS), the latter of which is accomplished via traditional laparoscopy or robotic-assisted surgery. Previously, MIS was routinely incorporated into the management of ESCC due to the approach's reduced operative morbidity and truncated hospital stay duration, but more recent clinical evidence has since impugned the efficacy of MIS because of the reportedly inferior disease-free survival and overall survival outcomes compared to open surgery. However, additional studies have documented equivalent outcomes among the various surgical modalities, suggesting further exploration of clinical factors as we endeavor to conclusively determine the standard of care for patients diagnosed with ESCC.

Outcomes after Surgical Treatment of Oesophagogastric Cancer with Synchronous Liver Metastases: A Multicentre Retrospective Cohort Study.

Approximately 10-12% of patients with oesophageal or gastric cancer (OGC) present with oligometastatic disease at diagnosis. It remains unclear if there is a role for radical surgery in these patients. We aimed to assess the outcomes of OGC patients who underwent simultaneous treatment for the primary tumour and synchronous liver metastases. Patients with OGC who underwent surgical treatment between 2008 and 2020 for the primary tumour and up to five synchronous liver metastases aiming for complete tumour removal or ablation (i.e., no residual tumour) were identified from four institutional databases. The primary outcome was overall survival (OS), calculated with the Kaplan-Meier method. Secondary outcomes were disease-free survival and postoperative outcomes. Thirty-one patients were included, with complete follow-up data for 30 patients. Twenty-six patients (84%) received neoadjuvant therapy followed by response evaluation. Median OS was 21 months [IQR 9-36] with 2- and 5-year survival rates of 43% and 30%, respectively. While disease recurred in 80% of patients (20 of 25 patients) after radical resection, patients with a solitary liver metastasis had a median OS of 34 months. The number of liver metastases was a prognostic factor for OS (solitary metastasis aHR 0.330; p-value = 0.025). Thirty-day mortality was zero and complications occurred in 55% of patients. Long-term survival can be achieved in well-selected patients who undergo surgical resection of the primary tumour and local treatment of synchronous liver metastases. In particular, patients with a solitary liver metastasis seem to have a favourable prognosis.

Thermal ablation versus liver resection for hepatocellular carcinoma in patients with cirrhosis: a systematic review and meta-analysis of propensity-score matched studies

The outcomes of cirrhotic patients with hepatocellular carcinoma (HCC) after thermal ablation (TA) versus liver resection (LR) are debated. We aimed to compare the overall survival (OS), disease-free survival (DFS), and operative outcomes after TA and LR for HCC in patients with cirrhosis. Until November 15, 2022, we searched PubMed, Embase, and Cochrane databases by using Medical Subject Heading terms and other terms, and used the Newcastle-Ottawa literature evaluation scale to assess the quality of selected studies. OS, DFS, and operative outcomes were extracted and analyzed. The meta-analysis showed that 5 propensity-score matched (PSM) studies including 933 patients (463 TA vs. 470 LR) were included. After analysis, TA and LR had similar results at 1-year OS (odds ratio [OR] 1.68; 95% confidence interval [CI] 1.01–2.78; P = 0.05) and 3-year OS (OR 0.76; 95% CI 0.56–1.04; P = 0.08), whereas LR increased 5-years OS (OR 0.37; 95% CI 0.18–0.74; P = 0.005). In addition to the DFS, the 1-year DFS was significantly higher in patients with LR. However, there were no obvious differences in 3-year and 5-year DFS when comparing TA and LR. The length of operative time and hospital stay were longer in the LR group. Besides, the LR group had significantly higher rate of perioperative blood transfusions and major complications. Our research proved that LR took advantage of OS and DFS for HCC patients with cirrhosis. Additional well-designed randomized controlled trials are needed.

Adoption of Total Neoadjuvant Therapy in the Treatment of Locally Advanced Rectal Cancer.

Local and metastatic recurrence are primary concerns following the treatment of locally advanced rectal cancer (LARC). Chemoradiation (CRT) can reduce the local recurrence rates and has subsequently moved to the neoadjuvant setting from the adjuvant setting. Pathological complete response (pCR) rates have also been noted to be greater in patients treated with neoadjuvant CRT prior to surgery. The standard approach to treating LARC would often involve CRT followed by surgery and optional adjuvant chemotherapy and remained the treatment paradigm for almost two decades. However, patients were often unable to complete adjuvant chemotherapy due to a decreased tolerance of chemotherapy following surgery, which led to upfront treatment with both CRT and chemotherapy, and total neoadjuvant therapy, or TNT, was created. The efficacy outcomes of local recurrence, disease-free survival, and pCR have improved in patients receiving TNT compared to the standard approach. Additionally, more recent data suggest a possible improvement in overall survival as well. Patients with a complete clinical response following TNT have the opportunity for watch-and-wait surveillance, allowing some patients to undergo organ preservation. Here, we discuss the clinical trials and studies that led to the adoption of TNT as the standard of care for LARC, with the possibility of watch-and-wait surveillance for patients achieving complete responses. We also review the possibility of overtreating some patients with LARC.

Short-term clinical outcomes and five-year survival analysis of laparoscopic-assisted transanal natural orifice specimen extraction versus conventional laparoscopic surgery for sigmoid and rectal cancer: a single-center retrospective study.

The cosmetic benefits of natural orifice specimen extraction (NOSE) are easily noticeable, but its principles of aseptic and tumor-free procedure have caused controversy. We conducted a retrospective analysis of the clinical data of patients who underwent laparoscopic-assisted transanal NOSE or conventional laparoscopic surgery (CLS) for sigmoid and rectal cancer at our hospital between January 2018 and December 2018. The study aimed to compare the general characteristics, perioperative indicators, postoperative complications, and five-year follow-up results between the two groups. A total of 121 eligible patients were enrolled, with 52 underwent laparoscopic-assisted transanal NOSE and 69 underwent CLS. There were no significant differences observed between the two groups in terms of gender, age, body mass index (BMI), TNM stage, etc. (P > 0.05). However, the NOSE group exhibited significantly shorter total incision length and longer operation time compared to the CLS group (P < 0.05). There were no statistically significant differences observed between the two groups in terms of positive rate of bacterial culture, incidence rates of intraabdominal infections or anastomotic leakage (P > 0.05). Furthermore, during follow-up period there was no statistically significant difference observed between these two groups concerning overall survival rate and disease-free survival outcomes (P > 0.05). The management of surgical complications in CLS is exemplary, with NOSE presenting a sole advantage in terms of incision length albeit at the cost of prolonged operative time. Therefore, NOSE may be deemed appropriate for patients who place high emphasis on postoperative cosmetic outcomes.