Difference In Overall Survival Research Articles

Construction of artificial neural network (ANN) based on predictive value of prognostic nutritional index (PNI) and neutrophil-to-lymphocyte ratio (NLR) in patients with cervical squamous cell carcinoma.

To explore the analytical worth of prognostic nutritional index (PNI) and neutrophil-to-lymphocyte ratio (NLR) in patients with cervical squamous cell carcinoma. The clinical data of 539 patients with cervical cancer in the Affiliated Tumor Hospital of Nantong University from December 2007 to October 2016 were analyzed retrospectively. The ROC is used to select the best cutoff values of PNI and NLR, which are 48.95 and 2.4046. Cox regression analysis was used for univariate and multivariate analysis. Survival differences were assessed by Kaplan-Meier (KM) survival method. Finally, a 3-layer artificial neural network (ANN) model is established. In cervical squamous cell carcinoma, the KM survival curve showed that the overall survival (OS) rate of high-level PNI group was significantly higher than that of low-level PNI group (P < .001), while the OS rate of low-level NLR group was significantly higher than that of high-level NLR group (P = .002). In non-squamous cell carcinoma, there was no significant difference in OS between the 2 groups (P > .005). According to Cox multivariate analysis, preliminary diagnosed PNI and NLR were independent prognostic factors of cervical squamous cell carcinoma (P < .001, P = .008), and pathological type and International Federation of Gynecology and Obstetrics (FIGO) stage also had a certain impact on tumor progression (P = .042, P = .048). The increase of PNI and the decrease of NLR will help patients with cervical squamous cell carcinoma live longer. ANN showed that PNI and NLR were of great importance in predicting survival. Preoperative PNI and NLR are independent predictors of cervical squamous cell carcinoma patients related to clinicopathological features, and have particular value in judging prognosis.

Phase II randomized trial comparing metronomic anthracycline-containing chemotherapy versus standard schedule in untreated HER2 negative advanced breast cancer: activity and quality of life results of the GOIM 21003 trial

BackgroundOptimizing chemotherapy to achieve disease and symptoms control is a noteworthy purpose in advanced breast cancer (ABC). We reported the activity and quality of life of a phase II study, comparing metronomic regimen with standard schedule as first line chemotherapy for ABC. MethodsPatients with HER2 negative ABC were randomized to non-pegylated liposomal doxorubicin (NPLD, 60 mg/m2 every 3 weeks) and cyclophosphamide (CTX, 600 mg/m2 every 3 weeks) (Arm A) or NPLD (20 mg/m2 day, on day 1, 8 and 15 every 4 weeks) and metronomic daily oral CTX 50 mg (ARM B). Primary end-points were overall response rate (ORR) and quality of life, secondary progression-free survival (PFS), overall survival (OS) and toxicity. ResultsFrom August 2012 to December 2017, 121 patients were enrolled, 105 evaluable. Median follow-up was 21.3 months. Most patients had hormone receptor positive. ORR was 43 % in arm A and 50 % in arm B. Median PFS was 8.9 months in arm A and 6,4 months in arm B. There was no difference in OS. Total score was not clinically different between the two arms. Grade 4 neutropenia was observed in 12 patients and 16 patients respectively; alopecia G2 in 41 % (77 %) vs 14 (27 %) in arm A and in arm B respectively. One cardiac toxicity was observed (arm A). ConclusionsFirst line metronomic chemotherapy for HER2 negative ABC had similar clinical activity and quite better tolerability than standard schedule and could be considered a further treatment option when chemotherapy is indicated.

Long-term outcomes of robot-assisted laparoscopic surgery versus conventional laparoscopic surgery for rectal cancer: single-center, retrospective, propensity score analyses

Although the short-term outcomes of robot-assisted laparoscopic surgery (RALS) for rectal cancer are well known, the long-term oncologic outcomes of RALS compared with those of conventional laparoscopic surgery (CLS) are not clear. This study aimed to compare the long-term outcomes of RALS and CLS for rectal cancer using propensity score matching. This retrospective study included 185 patients with stage I–III rectal cancer who underwent radical surgery at our institute between 2010 and 2019. Propensity score analyses were performed with 3-year overall survival (OS) and relapse-free survival (RFS) as the primary endpoints. After case matching, the 3-year OS and 3-year RFS rates were 86.5% and 77.9% in the CLS group and 98.4% and 88.5% in the RALS group, respectively. Although there were no significant differences in OS (p = 0.195) or RFS (p = 0.518) between the groups, the RALS group had slightly better OS and RFS rates. 3-year cumulative (Cum) local recurrence (LR) and 3-year Cum distant metastasis (DM) were 9.7% and 8.7% in the CLS group and 4.5% and 10.8% in the RALS group, respectively. There were no significant differences in Cum-LR (p = 0.225) or Cum-DM (p = 0.318) between the groups. RALS is a reasonable surgical treatment option for patients with rectal cancer, with long-term outcomes similar to those of CLS in such patients.

Efficacy of programmed cell death 1 inhibitor maintenance after chimeric antigen receptor T cells in patients with relapsed/refractory B-cell non-Hodgkin-lymphoma.

Chimeric antigen receptor (CAR)-T cells obtained long-term durability in about 30% to 40% of relapsed/refractory (r/r) B-cell non-Hodgkin lymphoma (B-NHL). Maintenance therapy after CAR-T is necessary, and PD1 inhibitor is one of the important maintenance therapy options. A total of 173 r/r B-NHL patients treated with PD1 inhibitor maintenance following CD19/22 CAR-T therapy alone or combined with autologous hematopoietic stem cell transplantation (ASCT) from March 2019 to July 2022 were assessed for eligibility for two trials. There were 81 patients on PD1 inhibitor maintenance therapy. In the CD19/22 CAR-T therapy trial, the PD1 inhibitor maintenance group indicated superior objective response rate (ORR) (82.9% vs 60%; P = 0.04) and 2-year progression-free survival (PFS) (59.8% vs 21.3%; P = 0.001) than the non-maintenance group. The estimated 2-year overall survival (OS) was comparable in the two groups (60.1% vs 45.1%; P = 0.112). No difference was observed in the peak expansion levels of CD19 CAR-T and CD22 CAR-T between the two groups. The persistence time of CD19 and CD22 CAR-T in the PD1 inhibitor maintenance group was longer than that in the non-maintenance group. In the CD19/22 CAR-T therapy combined with ASCT trial, no significant differences in ORR (81.4% vs 84.8%; P = 0.67), 2-year PFS (72.3% vs 74.9%; P = 0.73), and 2-year OS (84.1% vs 80.7%; P = 0.79) were observed between non-maintenance and PD1 inhibitor maintenance therapy groups. The peak expansion levels and duration of CD19 and CD22 CAR-T were not statistically different between the two groups. During maintenance treatment with PD1 inhibitor, all adverse events were manageable. In the multivariable analyses, type and R3m were independent predictive factors influencing the OS of r/r B-NHL with PD1 inhibitor maintenance after CAR-T therapy. PD1 inhibitor maintenance following CD19/22 CAR-T therapy obtained superior response and survival in r/r B-NHL, but not in the trial of CD19/22 CAR-T cell therapy combined with ASCT.

Emerging racial disparities among Medicare beneficiaries and Veterans with metastatic castration-sensitive prostate cancer.

Previous studies have shown that Black men receive worse prostate cancer care than White men. This has not been explored in metastatic castration-sensitive prostate cancer (mCSPC) in the current treatment era. We evaluated treatment intensification (TI) and overall survival (OS) in Medicare (2015-2018) and Veterans Health Administration (VHA; 2015-2019) patients with mCSPC, classifying first-line mCSPC treatment as androgen deprivation therapy (ADT) + novel hormonal therapy; ADT + docetaxel; ADT + first-generation nonsteroidal antiandrogen; or ADT alone. We analyzed 2226 Black and 16,071 White Medicare, and 1020 Black and 2364 White VHA patients. TI was significantly lower for Black vs White Medicare patients overall (adjusted odds ratio [OR] 0.68; 95% confidence interval [CI] 0.58-0.81) and without Medicaid (adjusted OR 0.70; 95% CI 0.57-0.87). Medicaid patients had less TI irrespective of race. OS was worse for Black vs White Medicare patients overall (adjusted hazard ratio [HR] 1.20; 95% CI 1.09-1.31) and without Medicaid (adjusted HR 1.13; 95% CI 1.01-1.27). OS was worse in Medicaid vs without Medicaid, with no significant OS difference between races. TI was significantly lower for Black vs White VHA patients (adjusted OR 0.75; 95% CI 0.61-0.92), with no significant OS difference between races. Guideline-recommended TI was low for all patients with mCSPC, with less TI in Black patients in both Medicare and the VHA. Black race was associated with worse OS in Medicare but not theVHA. Medicaid patients had less TI and worse OS than those without Medicaid, suggesting poverty and race are associated with care and outcomes.

1240 Assessing Survival Outcomes of PCV-Based and Temozolamide-Based Adjuvant Therapy in Oligodendroglioma Patients

INTRODUCTION: When treating oligodendroglioma patients, choosing between temozolomide (TMZ) and procarbazine, lomustine, and vincristine (PCV), with concurrent radiotherapy still poses a challenge. Given the commonality of tumor recurrence, optimizing progression-free survival while minimizing adverse effects is crucial to improving quality of life. METHODS: 87 patients treated for oligodendroglioma between 1994-2022 were retrospectively reviewed. Progression-free survival (PFS) and overall survival (OS) from initial resection were compared between PCV-based or TMZ-based treatment groups using Kaplan-Meier and multi-variable Cox survival analysis. RESULTS: The median age at diagnosis was 41 years and 62% were male. After initial resection, 42.8% received PCV-based treatment and 57.2% received TMZ-based treatment. Treatment groups were balanced in the following variables: age, tumor genetic profiling, the extent of resection, and KPS score. However, more patients in the TMZ-based group received concurrent radiation. The entire cohort had a 6.3-year PFS and 21.0-year OS. The median time to recurrence was significantly longer in those treated with PCV (12 years) compared to those treated with TMZ (4.7 years). PFS [HR = 0.46, p = 0.04] and OS [HR = 0.26, p = 0.04] were significantly longer in those receiving PCV-based treatment compared to TMZ-based treatment. After adjusting for previously mentioned variables, Cox regression analysis revealed no difference in OS between PCV- and TMZ-based treatment. The overall adverse effect rate did not significantly differ between PCV-based and TMZ-based treatment (25% vs. 28.1%, p &gt; 0.99). CONCLUSIONS: PCV treatment confers longer progression-free survival than TMZ treatment for oligodendroglioma patients, noting that most patients in our series received concurrent radiation with TMZ, and those receiving PCV not having received upfront radiation. As we anticipate the results of the CODEL trial, our findings suggest PCV-based therapy warrants consideration as the preferred therapeutic option for oligodendroglioma patients.

PCV Adjuvant Therapy as a Preferred Treatment Option for Oligodendroglioma Patients: A Comparative Study With Temozolomide and Concurrent Radiotherapy

INTRODUCTION: When treating oligodendroglioma patients, choosing between temozolomide (TMZ) and procarbazine, lomustine, and vincristine (PCV), with concurrent radiotherapy still poses a challenge. Given the commonality of tumor recurrence, optimizing progression-free survival while minimizing adverse effects is crucial to improving quality of life. METHODS: 87 patients treated for oligodendroglioma between 1994-2022 were retrospectively reviewed. Progression-free survival (PFS) and overall survival (OS) from initial resection were compared between PCV-based or TMZ-based treatment groups using Kaplan-Meier and multi-variable Cox survival analysis. RESULTS: The median age at diagnosis was 41 years and 62% were male. After initial resection, 42.8% received PCV-based treatment and 57.2% received TMZ-based treatment. Treatment groups were balanced in terms of age, tumor genetic profiling, extent of resection, or KPS score, however, the TMZ-based group had more patients receiving concurrent radiation. The entire cohort had a 6.3-year PFS and 21.0-year OS. The median time to recurrence was significantly longer in those treated with PCV (12 years) compared to those treated with TMZ (4.7 years). PFS [HR = 0.46, p = 0.04] and OS [HR = 0.26, p = 0.04] were significantly longer for those receiving PCV-based treatment compared to TMZ-based treatment. After adjusting for factors mentioned above, Cox regression analysis revealed no difference in OS between PCV- and TMZ-based treatment. The overall adverse effect rate did not significantly differ between PCV-based and TMZ-based treatment (25% vs. 28.1%, p &gt; 0.99). CONCLUSIONS: PCV confers improved progression-free survival than TMZ-based treatment for oligodendroglioma patients, noting that most patients in our series received concurrent radiation with TMZ, and those receiving PCV not having received upfront radiation. As we anticipate the results of the CODEL trial, our findings suggest PCV-based therapy warrants consideration as a preferred therapeutic option for oligodendroglioma patients.

The efficiency and safety of low-dose apatinib combined with oral vinorelbine in pretreated HER2-negative metastatic breast cancer.

Apatinib is an oral small-molecule tyrosine kinase inhibitor that blocks vascular endothelial growth factor receptor-2. Oral vinorelbine is a semisynthetic chemotherapeutic agent of vinorelbine alkaloids. Apatinib and oral vinorelbine have been proved to be effective in the treatment of metastatic breast cancer (mBC). At present, several small sample clinical trials have explored the efficacy of apatinib combined with oral vinorelbine in the treatment of mBC. This retrospective study included 100 human epidermal growth factor receptor-2 (HER2)-negative mBC patients who received low-dose apatinib (250 mg orally per day) plus oral vinorelbine until disease progression or intolerance during February 2017 and March 2023. The progression-free survival (PFS), overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR), disease control rate (DCR), and safety were analyzed by SPSS 26.0 software and GraphPad Prism 8 software. Cox proportional hazards regression model for univariate and multivariate was used to identify factors significantly related to PFS and OS. The median follow-up time for this study was 38.1 months. Among 100 patients with HER2-negative mBC, 66 were hormone receptor (HR)-positive/HER2-negative and 34 were triple-negative breast cancer (TNBC). The median PFS and OS were 6.0 months (95% CI, 5.2-6.8 months) and 23.0 months (95% CI, 19.9-26.1 months). There were no statistical differences in PFS (p = 0.239) and OS (p = 0.762) between the HR-positive /HER2-negative and TNBC subgroups. The ORR, CBR, and DCR were 21.0%, 58.0%, and 78.0%, respectively. Ninety-five patients (95.0%) experienced varying grades of adverse events (AEs) and 38.0% of patients for Grades 3-4. The most common Grades 3-4 AEs that we observed were neutropenia (30.0%) and leukopenia (25.0%). Low-dose apatinib combined with oral vinorelbine demonstrates potential efficacy and well tolerated for pretreated HER2-negative mBC.

Analysis of the efficacy and safety of hepatic arterial infusion chemotherapy for unresectable hepatitis B-related intrahepatic cholangiocarcinoma

Objective: To explore the efficacy and safety of hepatic arterial infusion chemotherapy(HAIC) for unresectable hepatitis B-related intrahepatic cholangiocarcinoma(ICC). Methods: This is a retrospective controlled study. Data from 140 unresectable ICC patients who received HAIC treatment at Sun Yat-sen University Cancer Center from March 2015 to June 2023 were retrospectively collected, including 72 patients in the hepatitis B surface antigen(HBsAg)negative group (43 males and 29 females, aged (59.6±9.5)years(range: 34 to 81 years)), 68 cases in the HBsAg-positive group (48 males, 20 females, aged (53.4±11.4)years(range: 29 to 82 years)). HAIC treatment used the FOLFOX regimen combined with oxaliplatin, leucovorin,and fluorouracil. The differences in effects, prognosis,and adverse reactions between the two groups of patients after HAIC treatment were analyzed. All variables were expressed as categorical data. The χ2 test or Fisher's exact probability method was used to compare between groups. The Kaplan-Meier method was used to draw survival curves. The difference of survival curve between groups were compared through the Log-rank test. Results: According to the Response Evaluation Criteria in Solid Tumors(RECIST) version 1.1,the objective response rate(ORR) of the HBsAg-negative group was 23.2%(16/69),and the ORR of the HBsAg-positive group was 40.3%(25/62). The difference in ORR between the two groups was statistically significant(χ2=4.459,P=0.035). According to the modified RECIST(mRECIST) criteria,the ORR of the HBsAg-negative group was 27.5%(19/69), and the ORR of the HBsAg-positive group was 45.2%(28/62). The difference in ORR between the two groups was statistically significant(χ2=4.410,P=0.036). The median progression-free survival(PFS) of the HBsAg-negative group and the positive group were 7.1 months(95%CI: 5.8 to 13.2 months) and 7.3 months (95%CI: 5.7 to 10.3 months), respectively, and the median overall survival(OS) were 16.3 months (95%CI: 12.5 to 33.9 months) and 15.9 months (95%CI: 9.2 to 20.7 months) respectively. There were no statistically significant differences in PFS and OS between the two groups (both P>0.05). The main serious adverse reactions of the two groups of patients included increased AST, increased ALT, thrombocytopenia,and neutropenia. There were no statistically significant differences in various adverse reactions between the two groups after HAIC treatment (all P>0.05). Conclusion: Patients with HBsAg-positive unresectable ICC are more likely to benefit from HAIC treatment.

Real-World Data on Pathological Response and Survival Outcomes After Neoadjuvant Chemotherapy in HER2-Low Breast Cancer Patients

BackgroundData on the pathological responses and survival outcomes after neoadjuvant chemotherapy (NACT) in human epidermal growth factor receptor-2 (HER2)-low breast cancer (BC) are lacking. This study aims to investigate this topic in the real world. MethodsClinicopathological data from 819 HER2-negative BC patients who underwent NACT between 2010 and 2020 were retrospectively retrieved from the Shanghai Jiaotong University Breast Cancer Database. These patients were categorized into HER2-low and HER2-0 groups. Logistic analyses were conducted to identify predictors of complete pathological response (pCR) and breast pCR. Cox regression analyses were conducted to assess the factors associated with disease-free survival (DFS) and overall survival (OS). Kaplan-Meier (K-M) curves were generated to compare DFS and OS between HER2-low BC and HER2-0 BC. ResultsOf the 819 BC patients, 669 (81.7%) had HER2-low tumors, and 150 (18.3%) had HER2-0 tumors. HER2-low BC had a significantly higher ratio of ER ≥ 10%, PR ≥ 20%, and Ki67 ≥ 15% than HER2-0 BC. A significantly higher breast pCR rate was observed in HER2-low BC than in HER2-0 BC (13.6% and 7.3%, respectively, P = .036). Age, HER2 status (low or 0), Ki67, and surgery options were associated with breast pCR in HER2-negative BC. In HER2-low BC, the pCR rate of ER ≥ 10% BC was significantly lower than that of ER < 10% BC, but the DFS and OS of ER 10% BC were significantly higher. The K-M curve showed no significant differences in DFS or OS between HER2-low and HER2-0 BC. Cox regression revealed that ER expression and histological grade (III vs. I∼II) were significantly associated with survival in HER2-low BC. ConclusionsIn this real-world data (RWD) study, a significantly higher breast pCR rate was found in HER2-low BC than in HER2-0 BC, although there was no significant difference in survival. Moreover, ER expression had a significant prognostic impact on HER2-low BC.

1237 The Mutational Landscape of Molecularly Defined Oligodendrogliomas

INTRODUCTION: Oligodendrogliomas are molecularly defined by IDH1/2 mutation and codeletion of chromosome arms 1p/19q. Prior studies identified capicua transcriptional repressor (CIC), far upstream binding protein (FUBP1), and the promoter region of telomerase reverse transcriptase (TERTp) as commonly mutated in oligodendrogliomas. However, prognostically relevant molecular signatures have yet to be identified. METHODS: A retrospective single-center study evaluated adults with pathologically confirmed IDH-mutant and 1p/19q co-deleted oligodendrogliomas that underwent surgery between 2005 and 2021. Genetic data from formalin-fixed, paraffin-embedded specimens were analyzed with the NGS Solid Tumor Panel at the Johns Hopkins Medical Laboratories, which tested over 400 genes. Kaplan-Meier curves and log-rank tests were used to compare progression-free survival (PFS) and overall survival (OS). Chi-squared tests compared clinical characteristics between mutation status in the ten most frequently mutated genes. RESULTS: From 277 patients with IDH-mutated, 1p/19q co-deleted oligodendrogliomas, 95 patients with NGS were included. Ten genes had 9 or more patients with a mutation, with CIC and FUBP1 being the most frequently mutated genes (n = 60 and n = 23, respectively). Kaplan-Meier curves showed that most genes were not associated with differences in PFS or OS. CIC conferred a reduction in PFS in patients with a PFS &lt;100 months (p = 0.038), though this significance was lost when including all PFS durations (p = 0.52). While no biomarkers had sufficient statistical power, our analysis showed trends in shortened survival in patients with TP53 (p = 0.01) and PIK3CA (p = 0.03) mutations. CONCLUSIONS: Oligodendrogliomas harbor frequent mutations in CIC, FUBP1, and TERTp, but most patients typically have minimal additional alterations. As NGS becomes routine, understanding these mutations may inform therapeutic and prognostic recommendations or the development of novel targeted therapies. Additional molecular assays beyond mutation analysis with NGS may reveal prognostically relevant biologic subgroups of oligodendrogliomas.

Durable Response to Enfortumab Vedotin Compared to Re-challenging Chemotherapy in Metastatic Urothelial Carcinoma After Checkpoint Inhibitors.

Enfortumab vedotin (EV), an antibody-drug conjugate targeting Nectin-4, has been used for patients with metastatic urothelial carcinoma (mUC) after progressing on checkpoint inhibitors (CPIs). Re-challenging chemotherapy with platinum agents and continuing CPIs beyond progressive disease (PD) have often been chosen following PD on CPIs, and several studies indicate favorable treatment effects of re-challenging chemotherapy. There is little evidence for comparing EV and re-challenging chemotherapy in real-world clinical practice. The aim was to reveal the real-world treatment outcomes of EV, re-challenging chemotherapy, and continuing CPIs beyond PD in mUC patients. A multi-institutional dataset of 350 mUC patients treated with CPIs was utilized. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and duration of response (DOR) were evaluated to compare the treatment arms. One hundred and nine mUC patients were treated with EV with a median follow-up of 6.4months. The ORR and disease control rate (DCR) were 48% and 70%, respectively. The OS from PD on pembrolizumab exhibited significant differences among the three groups, with a median OS of 8, 14, and 29months in continuing pembrolizumab beyond PD, re-challenging chemotherapy, and EV, respectively. When comparing the survival outcomes from the initiation of the treatment, there is neither a difference in OS (p=0.124), PFS (p=0.936), nor ORR (p=0.816) between EV and re-challenging chemotherapy. Notably, the DOR in patients who achieved an objective response was significantly longer in the EV group than the re-challenging chemotherapy group (a median of 11 and 5months, p=0.049). For OS, the difference was not statistically significant (27 and 11months in EV and re-challenging chemotherapy, respectively: p=0.05). A superior effect of EV on patient survival compared to re-challenging chemotherapy and continuing pembrolizumab beyond PD was observed in our real-world analysis, which is attributed to the durable DOR in EV treatment despite the similar ORR to re-challenging chemotherapy.

Locoregional recurrence and survival of breast-conserving surgery compared to mastectomy following neoadjuvant chemotherapy in operable breast cancer.

The risk of locoregional recurrence (LRR) and the long-term prognosis of breast-conserving surgery (BCS) after neoadjuvant chemotherapy (NAC) are still controversial. This study aimed to evaluate oncological outcomes for patients undergoing BCS after NAC and determine LRR and survival predictors. This study was a retrospective cohort study of patients with locally advanced breast cancer (LABC) who received NAC and underwent BCS or mastectomy from June 2011 to November 2020. LRR, disease-free survival (DFS), and overall survival (OS) were compared in patients undergoing BCS or mastectomy. Univariate and multivariate analyses were performed to determine LRR, DFS, and OS predictors. A total of 585 patients were included, of whom 106 (18.1%) underwent BCS and 479 (81.9%) underwent a mastectomy. The LRR rate was 11.3% in the BCS group and 16.3% in the mastectomy group, revealing no significant difference(p = 0.200). In patients who underwent BCS, clinical lymph node status, histological grade and pathological complete response (pCR) were independent factors to predict LRR. There was no significant difference in DFS and OS between the BCS and the mastectomy groups. Multivariable analysis showed that lymph node status, histological grade, molecular subtypes, pCR and Miller&Payne (M&P) classification were independent predictors of DFS. Lymph node status, molecular subtypes and pCR were independent predictors of OS. BCS or mastectomy was not an independent predictor of DFS or OS. Compared with mastectomy, BCS after NAC may not increase the risk of local recurrence or mortality, BCS can be performed in selected patients with small tumor size and good response to NAC.

Comparing surgical and endoscopic resection approaches for colorectal neuroendocrine tumors within the diameter range of 10-20mm: an inverse probability weighting analysis based on the SEER database.

Currently, the primary treatment modalities for colorectal neuroendocrine tumors (CRNET) with a diameter between 10mm and 20mm are surgical resection (SR) and endoscopic resection (ER). However, it remains unclear which surgical approach yields the greatest survival benefit for patients. This study included data from patients diagnosed with CRNET with tumor diameters ranging from 10mm to 20mm between the years 2004 and 2019, obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Patients were categorized into ER and SR groups based on the respective surgical approaches. Inverse probability weighting (IPTW) was employed to mitigate selection bias. Kaplan-Meier analysis and log-rank tests were utilized to estimate overall survival (OS) and cancer-specific survival (CSS). Cox regression analysis (univariate and multivariate) was performed to evaluate potential factors influencing survival. A total of 292 CRNET patients were included in this study (ER group: 108 individuals, SR group: 184 individuals). Prior to IPTW adjustment, Kaplan-Meier analysis and Cox proportional hazard regression analysis demonstrated that the OS and CSS of the SR group were inferior to those of the ER group. However, after IPTW adjustment, no statistically significant differences in prognosis were observed between the two groups. Subgroup analyses revealed that patients with muscular invasion, positive lymph nodes, or distant metastasis derived greater survival benefits from SR. Significant differences in OS and CSS between the two groups were also observed across different age groups. For patients with mucosal-limited lesions and without local lymph node or distant metastasis, ER is the preferred surgical approach. However, for patients with muscular invasion or positive lymph nodes/distant metastasis, SR offers a better prognosis. The choice of surgical approach should be based on the specific clinical characteristics of patients within different subgroups.

Evaluation of AJCC staging system and proposal of a novel stage grouping system in retroperitoneal liposarcoma: the Fudan Zhongshan experience.

Overall survival (OS) varies significantly among individuals with heterogeneous retroperitoneal liposarcoma (RPLS), even among those with the same clinical stage. Improved staging of RPLS is a critical unmet need, given the disappointing results of external validations of the 8th American Joint Committee on Cancer (AJCC) TNM staging system. The cohort study included 220 consecutive patients who underwent surgical resection for primary RPLS at the largest sarcoma centre of Fudan University in China from September 2009 to August 2021, combined with 277 adult patients with RPLS in the SEER database from 1975 to 2020. Data analysis was performed from December 2021 to December 2022. Patients were retrospectively restaged according to the 8th and 7th editions of the TNM staging system as well as the new TNM (nTNM) staging system. The primary endpoint was overall survival (OS). Comparative analysis of postoperative survival was performed using the Kaplan-Meier method, and differences between subgroups were tested using the log-rank test. The OS prediction nomogram was generated based on baseline variables and tumour characteristics. Harrell's consistency index (C-index), area under the curve (AUC) of receiver operating characteristic curves (ROC), and calibration curves were used to evaluate the performance of the nomogram. A total of 497 patients were enrolled in the study, including 282 (56.7%) male patients. The median follow-up was 51 months (interquartile range, IQR, 23-83), and the OS rates at 1, 3, and 5 years were 87.9%, 75.3%, and 64.9%, respectively. According to the staging distribution of the AJCC 7th edition, 6 patients were stage IA (1.2%), 189 patients were stage IB (38%), 12 patients were stage IIA (2.4%), 150 patients were stage IIB (30.1%), 131 patients were stage III (26.3%), and 9 patients were stage IV (1.8%). With the 8th edition staging, this distribution changed: 6 patients (1.2%) were stage IA, 189 patients (38%) were stage IB, 12 patients (2.4%) were stage II, 24 patients (4.8%) were stage IIIA, 257 patients (51.7%) were stage IIIB, and 9 patients (1.8%) were stage IV. 182 patients (36.6%) were reclassified according to the nTNM staging system with the new T stage classification. The C-index and log-rank score improved after implementation of nTNM implementation. The nTNM system was associated with improved identification of high-risk patients compared with the AJCC 7th and 8th TNM. The FNCLCC stage proved to be highly prognostic with significant intergroup differences in OS. The calibration curve shows a high degree of agreement between the actual OS rate and the nomogram estimated OS rate. Compared with 8th AJCC TNM, 7th AJCC TNM staging system showed a more homogeneous staging distribution and a slight improvement in the prognostic accuracy of RPLS. The revised T-stage and nTNM systems showed better risk stratification performance. The FNCLCC stage was found to have high prognostic value, further emphasising histological grade is the least negligible prognostic factor in predicting patient survival. The constructed nomogram model enables individualized prognostic analysis and helps to develop risk-adapted therapy for RPLS patients.

Change in the Neutrophil-to-Eosinophil Ratio After Avelumab Maintenance for Advanced Urothelial Carcinoma: The UROKYU Study.

The association between clinical outcomes and posttreatment changes in the neutrophil-to-lymphocyte ratio (NLR) and neutrophil-to-eosinophil ratio (NER) in patients receiving avelumab maintenance therapy for advanced urothelial carcinoma (UC) is unclear. We retrospectively analyzed data from advanced UC patients who received avelumab and had not progressed with first-line platinum-based chemotherapy. The association between the changes in NLR and NER from pretreatment to week 6 of avelumab treatment and therapeutic efficacy was evaluated. Thirty-two patients were enrolled in this study (male, n=25; female, n=7; median age, 71 years). At six weeks, 19 patients (59.4%) had a decreased NLR and 18 patients (56.3%) had a decreased NER. When the change in NER from pretreatment to six weeks was compared, there was a significant decrease in responders (without progressive disease) (p=0.008); however, there was no significant decrease in non-responders (progressive disease) (p=0.855). The NLR showed no significant change in either group (p=0.099, 0.358). When patients were compared according to the change in the NLR at six weeks, progression-free survival (PFS) and overall survival (OS) did not differ between the decreased NLR and increased NLR groups (p=0.116, 0.256). When patients were compared according to the change in the NER, the decreased and increased groups showed significant differences in PFS and OS (p<0.001, 0.030). In the present real-world study, the responders showed a significantly decreased NER at six weeks. This was associated with improved PFS and OS in patients with advanced UC.

Long-Term Outcomes of Robotic Versus Laparoscopic Total Mesorectal Excisions: A Propensity-Score Matched Cohort study of 5-year survival outcomes.

To compare long-term outcomes between laparoscopic and robotic total mesorectal excisions (TMEs) for rectal cancer in a tertiary center. Laparoscopic rectal cancer surgery has comparable long-term outcomes to the open approach, with several advantages in short-term outcomes. However, it has significant technical limitations, which the robotic approach aims to overcome. We included patients undergoing laparoscopic and robotic TME surgery between 2013 and 2021. The groups were compared after propensity-score matching. The primary outcome was 5-year overall survival (OS). Secondary outcomes were local recurrence (LR), distant recurrence (DR), disease-free survival (DFS), and short-term surgical and patient-related outcomes. A total of 594 patients were included, and after propensity-score matching 215 patients remained in each group. There was a significant difference in 5-year OS (72.4% for laparoscopy vs 81.7% for robotic, P = 0.029), but no difference in 5-year LR (4.7% vs 5.2%, P = 0.850), DR (16.9% vs 13.5%, P = 0.390), or DFS (63.9% vs 74.4%, P = 0.086). The robotic group had significantly less conversion (3.7% vs 0.5%, P = 0.046), shorter length of stay [7.0 (6.0-13.0) vs 6.0 (4.0-8.0), P < 0.001), and less postoperative complications (63.5% vs 50.7%, P = 0.010). This study shows a correlation between higher 5-year OS and comparable long-term oncological outcomes for robotic TME surgery compared to the laparoscopic approach. Furthermore, lower conversion rates, a shorter length of stay, and a less minor postoperative complications were observed. Robotic rectal cancer surgery is a safe and favorable alternative to the traditional approaches.

Resection status and margin control in intraoperative frozen sectioning analysis of oral squamous cell carcinoma.

Intraoperative frozen section analysis (IFSA) is a well-established procedure for determining the intraoperative soft tissue resection status in patients with oral squamous cell carcinoma (OSCC). Margin status is a major predictor of the patient´s outcome, histologically free margins of ≥ 5mm are demanded. This study evaluates the accuracy of IFSA, the impact of margin status and the impact of intraoperative margin revision on disease-free survival (DFS) and overall survival (OS). This retrospective study included 213 patients with OSCC. IFSA results were compared with definitive histopathological reports, Kaplan-Meier analysis was performed. Cut-off values were calculated for resection margins considering known risk factors. IFSA showed positive margins in 8 cases (3.8%). Kaplan-Meier analysis revealed no significant differences for OS or DFS if R0-status was achieved by initial resection or immediate re-resection. Final histopathological evaluation revealed false-positive IFSA in 3/8 cases (37.5%) and false-negative IFSA in 1/205 cases (0.5%). Sensitivity was 83.3% and specificity was 98.6%. Analysis of optimal cut-off values showed no general need for larger resection margins in patients with risk factors. Cut-off values were slightly higher for patients with the risk factor alcohol consumption (7mm for OS and DFS) or pN + ECS- disease (7mm for DFS). Optimal cut-off values for tumour-margin-distance were around 6mm. IFSA provides a valuable assessment method for intraoperative soft tissue resection margins. Risk factors seemingly do not significantly influence the extent of tumour resection.

Abstract 379: Landscape of HIF-1α expression across 24,186 solid tumors using comprehensive immune profiling

Abstract Background: Transcription factor Hypoxia Inducible Factor-1α (HIF-1α) is a key regulator of various cellular and systemic responses to hypoxia, with HIF-1α mediated pathways playing an important role in tumor progression and metastasis. Recent studies have highlighted the correlation between HIF-1α expression with tumor cell survival, angiogenesis, and invasion. In this study, we explore the landscape of HIF-1α expression across 35 solid tumor histologies, its co-expression with immune checkpoint and angiogenesis-related genes, as well as its association with outcomes from a retrospective cohort of patients with non-small cell lung cancer (NSCLC) treated with pembrolizumab. Methods: A discovery cohort of 24,186 solid tumors across 35 types were evaluated by comprehensive immune profiling assay. HIF-1α gene expression was normalized and ranked against a reference population of 735 samples yielding a percentile rank values [0-100], with rank classified as high (≥75), moderate (≥25 and &amp;lt;75) and low (&amp;lt;25). We investigated the distribution of HIF-1α expression, cellular proliferation signature, and co-expression with other immunotherapy targets using Spearman correlations (rs). Additionally, Kaplan-Meier analysis and Chi-squared tests were utilized for overall survival (OS), progression free survival (PFS) and objective response rate (ORR) differences in a retrospective cohort of 72 patients with NSCLC, treated with pembrolizumab. Results: Pan-cancer analysis confirmed a broad distribution of HIF-1α expression, with highest median expression levels observed in brain and central nervous system (CNS) (median=64), thyroid (median=49) and uterine (median=42) cancers. Significant associations (p&amp;lt;0.001) were observed between PD-L1 positivity (TPS≥1%, CPS≥1) and HIF-1α expression, with 60% of HIF-1α high cases (n=1,314/2,193) being PD-L1 positive, whereas 53% of HIF-1α low cases (n=4,834/9,135) were PD-L1 negative. Significant correlations (p&amp;lt;0.05) of ranked expression of HIF-1α with immune checkpoint blockage targets like PD-1 and CTLA-4, as well as angiogenesis-related genes like VEGFA and PTEN were observed. Within our pembrolizumab-treated retrospective cohort, there were no significant differences in OS and PFS between HIF-1α high and HIF-1α low tumors. However, the response to pembrolizumab was significantly higher in HIF-1α low tumors (ORR=58.82%, p&amp;lt;0.01) compared to HIF-1α high tumors. Conclusion: In clinically tested solid tumors, HIF-1α showed a dynamic expression range, with highest levels observed in brain, thyroid and uterine cancers. Significant co-expression of HIF-1α with various downstream genes, especially angiogenesis-related genes, enabled identification of gene signatures that characterize the hypoxic tumor microenvironment and may aid in the development of novel combination therapy strategies. Citation Format: Hardik I. Parikh, Sarabjot Pabla, Maria-Fernanda Senosain, Robert Seager, Erik Vanroey, Shuang Gao, Yamuna Pulivendula, Paul DePietro, Mary Nesline, Durgapras Dash, Jeffrey Conroy, Stephanie Hastings, Heidi Ko, Kyle Strickland, Rebecca Previs, Eric Severson, Taylor Jensen, Shakti Ramkissoon, Marcia Eisenberg, Brian Caveney. Landscape of HIF-1α expression across 24,186 solid tumors using comprehensive immune profiling [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 379.

Abstract 5201: Characterization of PDLIM2 in non-small cell lung cancer

Abstract Introduction: PDZ and LIM domain protein 2 (PDLIM2) acts as tumor suppressor by downregulating NF-κB and STAT3 signaling, modulating inflammation, immune response, and cell survival. Mouse model studies have demonstrated that downregulation of PDLIM2 leads to PD-1 immune blockade and chemotherapy resistance. We present a large clinical and molecular characterization of PDLIM2 expression in non-small cell lung cancer (NSCLC). Methods: NextGen sequencing of DNA (whole exome)/RNA (whole transcriptome) was performed for NSCLC (Total N = 29126; Adenocarcinoma [-A, N = 15765], Squamous [-S, N = 6416]) patient tumors submitted to Caris Life Sciences (Phoenix, AZ). Mutations were defined as pathogenic SNVs/indels. Samples were stratified by PDLIM2 expression quartiles (in transcripts per million [TPM]) for all NSCLC tumors (Q4: H, Q1: L). PD-L1 expression [22C3; Positive (+): tumor proportion score (TPS) ≥1%]was assessed by IHC. High tumor mutational burden (TMB-high) set as ≥10 mutations per Mb. Cell infiltration in the tumor microenvironment was estimated by QuantiSEQ. Gene expression profiles were analyzed for transcriptional signatures predictive of response to immunotherapy (T cell-inflamed). Real-world overall survival was assessed from insurance claims data and Kaplan-Meier estimates were calculated for molecularly defined subpopulations. Mann-Whitney U and X2/Fisher-Exact tests were applied where appropriate, with P-values adjusted for multiple comparisons (p &amp;lt; 0.05). Results: Median PDLIM2 expression was higher in NSCLC-A compared to NSCLC-S (15.3 vs 13.6 TPM, p &amp;lt; 0.001). PDLIM2-AL had a lower prevalence of EGFR mutations than PDLIM2-AH (15.5% vs 19.4%, p &amp;lt; 0.01), but the opposite pattern was observed for STK11 (21.5% vs 11.2%), RB1 (7.5% vs 3.8%), TP53 (62.9% vs 52.8%), KEAP1 (18.4% vs 10.9%), and SMARCA4 (9.15 vs 4.5%) alterations (all p &amp;lt; 0.001). PDLIM2-AL tumors had decreased PD-L1+ (L: 52.4% vs H: 58.4% p &amp;lt; 0.001) but increased TMB-High status (L: 40.9% vs H: 28.5%, p &amp;lt; 0.001). PD-L1+ and TMB-H frequency did not vary with PDLIM2 expression in NSCLC-S. In both NSCLC-A and -S tumors, PDLIM2H had increased infiltration of NK cells, macrophages, dendritic cells, T cells, neutrophils, monocytes, and B cells compared to PDLIM2L (all p &amp;lt; 0.05), in addition to increased T cell-inflammed scores (p &amp;lt; 0.001). PDLIM2-AH was associated with improved overall survival (OS) (median 21.7 vs L: 15.6 months; p &amp;lt; 0.001; Hazard ratio [HR] = 0.825, 95% Confidence Interval [CI] 0.765 - 0.889) and time on pembrolizumab treatment (median 6.2 vs L: 5.6 months; p = 0.009; HR = 0.825 95% CI 0.714 - 0.953). No difference in OS was observed between PDLIM2-SH vs L tumors (H: 14.8 vs L: 14.0 months; p = 0.37; HR = 0.95, CI 0.85-1.06). Conclusions: NSCLC-A with high PDLIM2 expression have a unique mutational profile, increased immune cell infiltration and favorable OS. Therapeutic strategies for targeting PDLIM2 to modulate NF-κB and STAT3 signaling should be further explored. Citation Format: Karam Ashouri, Harris Krause, Andrew Elliott, Stephen V. Liu, Patrick C. Ma, Balazs Halmos, Zhaoxia Qu, Gutian Xiao, Ari Vanderwalde, Jorge J. Nieva. Characterization of PDLIM2 in non-small cell lung cancer [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 5201.