Median Recurrence-free Survival Research Articles

Surgical outcome and risk scoring to predict survival after hepatic resection for hepatocellular carcinoma with portal vein tumor thrombosis.

The hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is classified as the advanced stage (BCLC stage C) with extremely poor prognosis, and in current guidelines is recommended for systemic therapy. This study aimed to evaluate the surgical outcomes and long-term prognosis after hepatic resection (HR) for patients who have HCC combined with PVTT. We retrospectively analyzed 332 patients who underwent HR for HCC with PVTT at ten tertiary referral hospitals in South Korea. The median overall and recurrence-free survival after HR were 32.4 and 8.6 months, while the 1-, 3-, and 5-year overall survival rates were 75%, 48%, and 39%, respectively. In multivariate analysis, tumor number, tumor size, AFP, PIVKA-II, neutrophil-to-lymphocyte ratio, and albumin-bilirubin (ALBI) grade were significant prognostic factors. The risk scoring was developed using these seven factors-tumor, inflammation and hepatic function (TIF), to predict patient prognosis. The prognosis of the patients was well stratified according to the scores (log-rank test, p < 0.001). HR for patients who have HCC combined with PVTT provided favorable survival outcomes. The risk scoring was useful in predicting prognosis, and determining the appropriate treatment strategy for those patients who have HCC with PVTT.

Hyperthermic intraperitoneal chemotherapy in colorectal cancer.

This study evaluated the efficacy of hyperthermic intraperitoneal chemotherapy (HIPEC) in colorectal cancer with peritoneal metastases (pmCRC) in a large international data set of patients. Patients with pmCRC from 39 centres who underwent cytoreductive surgery with HIPEC between 1991 and 2018 were selected and compared for the HIPEC protocols received-oxaliplatin-HIPEC versus mitomycin-HIPEC. Following analysis of crude data, propensity-score matching (PSM) and Cox-proportional hazard modelling were performed. Outcomes of interest were overall survival (OS), recurrence-free survival (RFS) and the HIPEC dose-response effects (high versus low dose, dose intensification and double drug protocols) on OS, RFS and 90-day morbidity. Furthermore, the impact of the treatment time period was assessed. Of 2760 patients, 2093 patients were included. Median OS was 43 months (95% c.i. 41 to 46 months) with a median RFS of 12 months (95% c.i. 12 to 13 months). The oxaliplatin-HIPEC group had an OS of 47 months (95% c.i. 42 to 53 months) versus 39 months (95% c.i. 36 to 43 months) in the mitomycin-HIPEC group (P = 0.002), aHR 0.77, 95% c.i. 0.67 to 0.90, P < 0.001. The OS benefit persisted after PSM of the oxaliplatin-HIPEC group and mitomycin-HIPEC group (48 months (95% c.i. 42 to 59 months) versus 40 months (95% c.i. 37 to 44 months)), P < 0.001, aHR 0.78 (95% c.i. 0.65 to 0.94), P = 0.009. Similarly, matched RFS was significantly higher for oxaliplatin-HIPEC versus others (13 months (95% c.i. 12 to 15 months) versus 11 months (95% c.i. 10 to 12 months, P = 0.02)). High-dose mitomycin-HIPEC protocols had similar OS compared to oxaliplatin-HIPEC. HIPEC dose intensification within each protocol resulted in improved survival. Oxaliplatin + irinotecan-HIPEC resulted in the most improved OS (61 months (95% c.i. 51 to 101 months)). Ninety-day mortality in both crude and PSM analysis was worse for mitomycin-HIPEC. There was no change in treatment effect depending on the analysed time period. Oxaliplatin-based HIPEC provided better outcomes compared to mitomycin-based HIPEC. High-dose mitomycin-HIPEC was similar to oxaliplatin-HIPEC. The 90-day mortality difference favours the oxaliplatin-HIPEC group. A trend for dose-response between low- and high-dose HIPEC was reported.

Clinical outcomes of transarterial chemoembolization in Child-Turcotte Pugh class A patients with a single small (≤3cm) hepatocellular carcinoma.

Transarterial chemoembolization (TACE) is one of the standard modalities used to treat unresectable hepatocellular carcinoma (HCC), but the effectiveness of TACE for treating patients with a solitary small (≤3cm) HCC and well-preserved liver function has not been definitively established. This study aimed to determine the therapeutic impact of TACE in patients with these characteristics. This multicenter (four university hospitals) retrospective cohort study analyzed the medical records of 250 patients with a solitary small (≤3cm) HCC and Child-Turcotte-Pugh (CTP) class A liver function diagnosed over 10years. Posttreatment outcomes, including overall survival (OS), recurrence-free survival (RFS), and adverse events, were assessed following TACE therapy. One hundred and thirty-eight of the 250 patients (55.2%) treated with TACE achieved complete remission (CR). Overall median OS was 77.7months, and median OS was significantly longer in the CR group than in the non-CR group (89.1 vs. 58.8months, P=0.001). Median RFS was 19.1months in the CR group. Subgroup analysis identified hypertension, an elevated serum albumin level, and achieving CR as significant positive predictors of OS, whereas diabetes, hepatitis c virus infection, and tumor size (>2cm) were poor prognostic factors of OS. The study demonstrates the effectiveness of TACE as a viable alternative for treating solitary small (≤3cm) HCC in CTP class A patients.

Abstract PO2-16-11: Real-World Data of Neuroendocrine Neoplasms of Breast

Abstract Background: Primary neuroendocrine neoplasms (NEN) of breast are rare and heterogeneous. WHO has classified NENs of non-endocrine organs into three distinct categories in 2022, however real-world data on outcomes of patients with NENs of non-endocrine organs under this new classification system are still sparse. Real world experience regarding demography, clinical presentation, treatment response, and prognosis can help identify potential areas of improvement in the management of breast NEN. Methods: Here, we present our findings from patients with NEN of breast in the Cleveland Clinic Foundation between 2000 and 2023. Pathology reports were reviewed to confirm NEN of breast origin. Neuroendocrine differentiation was determined by tumor histology and immunohistochemistry (IHC). For metastatic tumors at presentation, primary organ was determined by IHC and clinical presentation. Overall survival (OS) was from date of diagnosis of NEN. Recurrence is redemonstration of tumor following curative intent therapy, and progression is increase in tumor burden. T-test and log-rank test were used in statistical analyses. Results: Total of 97 patients were identified. Of these, 79 presented with localized disease, 18 were metastatic at presentation. 88 (91%) were invasive ductal carcinoma (IDC), and 64 (81%) were local disease at presentation and rest were metastatic. Gender spread was 92:5 (F:M). Patients with ER + disease was 84/96, PR + disease was 71, and 4/93 patients had overexpression of HER2. Median age was 70 at diagnosis. 11 patients underwent neoadjuvant chemotherapy, 15 patients underwent adjuvant chemotherapy (AC), and 58/84 patients underwent hormonal adjuvant therapy. For localized disease, median recurrence free survival (RFS) was 165 months (144-NA), and recurrence rate was 8/79 (10%). Recurrence rate for local IDC was 10% (6/64). Patients with metastatic disease at presentation had a median progression free survival (PFS) of 30 months, and progression rate was 7/18 (39%). For patients with metastatic disease, median lines of palliative therapy used was 2, with median duration of first line treatment being 3.5 months, and 10 months for second line. Most common surgical procedure was mastectomy, with 37% of patients undergoing management. Median duration from diagnostic biopsy to definitive surgery was 1 month. Median follow up was 28 months. Most common hormonal adjuvant option was anastrozole (58%), most common AC regimen was docetaxel and cyclophosphamide (39%), and most common first line palliative agent was letrozole (42%). Patients who underwent AC did not reach median OS, and patients who did not receive AC had a median OS of 148 months (p=0.8). Patients with grade 3 tumors had a median OS of 58.6 months, and grade 1 and 2 had a median OS of 148.1 months (p=0.5). Discussion: Current treatment strategies for NEN of breast mirror those of non-NEN of breast with similar histology and stage based on extrapolation of data. Recurrence rate was similar between IDC and SPC. In our cohort, survival was not significantly dependent on grade and use of AC. This might be due to the number of patients included in our study, as there was a non-significant trend towards lower OS in patients with high-grade neoplasms, and further limitations from retrospective design of study. Further research towards benefit of AC in NEN of breast and prognostic value of grading is necessary to explore management options in comparison to non-NEN of the breast. Citation Format: Serhan Unlu, Olisaemeka Ogbue, Gloria Lewis, Abdo Haddad, Hamed Daw, Baidehi Maiti. Real-World Data of Neuroendocrine Neoplasms of Breast [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 PO2-16-11.

Abstract PO4-03-05: Prognostic value of Ki67 expression in post-treatment tumors of patients with residual triple-negative breast cancer after neoadjuvant chemotherapy

Abstract Introduction Patients with triple-negative breast cancer (TNBC) who do not achieve pathological complete response (pCR) against neoadjuvant chemotherapy (NAC) have a poor prognosis. The prognosis of these patients can be differentiated using various parameters, including the Residual Cancer Burden (RCB) index and tumor-infiltrating lymphocytes. In this study, we took a different angle and aimed to evaluate the prognostic value of post-treatment Ki67 expression, which was examined in tumors following NAC in patients with non-pCR TNBC. Methods A retrospective review of clinical records from February 2008 to December 2021 was conducted of patients from Gangnam Severance Hospital and Asan Medical Center, both in Seoul, South Korea. We included patients with non-metastatic TNBC who underwent NAC including anthracycline and taxane regimens, followed by curative surgery, regardless of adjuvant capecitabine receipt. Ki67 expression and the RCB index were evaluated using residual tumors obtained from surgery. High Ki67 expression was defined as ≥20%. The 5-year recurrence-free survival (RFS) was estimated using Kaplan-Meier analysis, and hazard ratios (HR) were calculated using Cox regression analysis. Results This study included 338 patients with available Ki67 expression data in residual tumors. Among them, 110 patients (30.9%) had low Ki67 expression, while 228 patients (64%) had high Ki67 expression. At a median follow-up of 34 months, those with low Ki67 expression had a 5-year RFS rate of 82.6%, while those with high Ki67 expression had a rate of 58.3%, with a HR of 0.345 (95% CI 0.210-0.565, p&amp;lt; 0.001). When stratified by the RCB index, the 5-year RFS of RCB-I patients was 93%, RCB-II patients 70.2%, and RCB-III patients 40.5%. When assessing survival outcomes based on both Ki67 expression and the RCB index, patients with RCB-I and low Ki67 (n=26) had a 100% 5-year RFS rate. Patients with RCB-I and high Ki67 (n=24) had a rate of 83.3%. Notably, in patients with RCB-III and high Ki67 (n=62), the 5-year RFS rate was 35.5% and there was no significant difference in RFS based on the receipt of adjuvant capecitabine (median RFS: capecitabine - 18 months, observation - 15 months, p-value=0.994). Conclusions Our findings demonstrate the prognostic value of Ki67 expression in residual TNBC after NAC, indicating that cases with low Ki67 expression have a favorable outcome. Combining Ki67 expression with the RCB index allows identification of patients with good residual disease (i.e. low Ki67 expression and RCB-I) who could be potential candidates for de-escalating adjuvant treatments such as capecitabine or pembrolizumab. However, for patients with high Ki67 expression and RCB-III, novel strategies are required to improve survival outcomes beyond the use of capecitabine. Citation Format: Yoonwon Kook, Soo-Young Lee, Seung Ho Baek, Min Ji Kim, Junghyun Kim, Sohyun Moon, Seung Eun Lee, Soong June Bae, Joon Jeong, Sae Byul Lee, Sung Gwe Ahn. Prognostic value of Ki67 expression in post-treatment tumors of patients with residual triple-negative breast cancer after neoadjuvant chemotherapy [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 PO4-03-05.

Adjuvant chemotherapy is associated with better oncological outcomes after ALPPS for colorectal liver metastases.

ALPPS enables complete tumor resection in a shorter interval and a larger number of patients than classic two-stage hepatectomies. However, there is little evidence regarding long-term outcomes in patients with colorectal liver metastases (CLM). This study aims to evaluate the short and long-term outcomes of ALPPS in patients with CRM. Single-cohort, prospective, observational study. Patients with unresectable CLM due to insufficient liver remnant who underwent ALPPS between June 2011 and June 2021 were included. Of 32 patients treated, 21 were male (66%) and the median age was 56years (range = 29-81). Both stages were completed in 30 patients (93.7%), with an R0 rate of 75% (24/32). Major morbidity was 37.5% and the mortality nil. Median overall survival (OS) and recurrence-free survival (RFS) were 28.1 and 8.8months, respectively. The 1-3, and 5-year OS was 86%, 45%, and 21%, and RFS was 42%, 14%, and 14%, respectively. The only independent risk factor associated with poor RFS (5.7 vs 11.6months; p = 0.038) and OS (15 vs 37months; p = 0.009) was not receiving adjuvant chemotherapy. KRAS mutation was associated with worse OS from disease diagnosis (24.3 vs. 38.9months; p = 0.025). ALPPS is associated with favorable oncological outcomes, comparable to traditional strategies to increase resectability in patients with CLM and high tumor burden. Our results suggest for the first time that adjuvant chemotherapy is independently associated with better short- and long-term outcomes after ALPPS. Selection of patients with KRAS mutations should be performed with caution, as this could affect oncological outcomes.

Predictive and Prognostic Factors Related to Chemoradioresistance in Neoadjuvant Treatment of Locally Advanced Rectal Cancer at Panama

&amp;lt;i&amp;gt;Background:&amp;lt;/i&amp;gt; In Panama, and the rest of Latin America, there are few publications on chemoradioresistance, it leads to poor prognosis and represents the main reason for failure of therapy, ultimately it can lead to tumor recurrence and metastasis. &amp;lt;i&amp;gt;Objective:&amp;lt;/i&amp;gt; Identify factors associated with chemoradioresistance in the neoadjuvant treatment of locally advanced rectal cancer at the Instituto Oncológico Nacional de Panamá, period 2016-2020. Methodology: This retrospective study included 71 patients with LARC who received neoadjuvant chemoradiotherapy and surgery. Chemoradioresistant patients were those who did not reach a higher pathological stage of ypT2NO and the results were compared. &amp;lt;i&amp;gt;Results:&amp;lt;/i&amp;gt; Of the 71 patients, pathological complete response (pCR) was achieved in 34 patients (48%). 49% of patients met chemoradioresistance criteria. In this group, the median CEA was 136 ng/ml, the median hemoglobin was 12 g/dl, and the median BMI was 26 kg/m2. The median radiation dose was 5000Gy. The time between completion of chemoradiotherapy and surgery was 110 days (16 weeks). Depending on the type of surgery, 65% who underwent low anterior resection were chemoradioresistant. The variables with statistical significance were the CEA value &amp;gt;5 ng/mL (OR=1.81, p=0.026) prior to the start of neoadjuvant treatment, with a lower pCR rate. Likewise, the ECOG scale (OR=2.51, p=0.015) was a risk factor related to chemoradioresistance, the lower the ECOG, the lower the risk of chemoradioresistance. The median overall survival and median recurrence-free survival was not reached in both groups and there was no statistically significant difference. &amp;lt;i&amp;gt;Conclusions:&amp;lt;/i&amp;gt; Significant interactions were identified between CEA levels prior to the start of neoadjuvant treatment with the pathological complete response rate and the ECOG score with chemoradioresistance. Therefore, these factors can be used to predict patient outcomes, will help optimize personalized treatment strategies and improve patient outcomes.

Role of adjuvant therapy in resected periampullary adenocarcinoma: A propensity matched case-control study.

The published data had contradictory information on the role of adjuvant therapy on resected periampullary carcinomas (PACA). The study was performed to evaluate the survival benefit of adjuvant treatment. This was a propensity score matched case-control study from a prospectively maintained database from 2004-2019. The study included patients with nonpancreatic PACA who underwent curative resection. The patients (cases) who received adjuvant chemotherapy were compared with patients (controls) who were observed alone after surgery. Of 510 patients with PACA, 230 patients (cases = 107, controls = 123) formed the unmatched study cohort. After propensity score matching, 140 patients (cases = 70, controls = 70) formed the matched study cohort. The median overall survival (OS) was similar in cases than controls in the unmatched population but doubled non-significantly in cases after matching (unmatched population, 54 months vs. 54 months, p-value = 0.624; matched population, 71 months vs. 36 months, p-value = 0.087). However, the median recurrence-free survival (RFS) was non significantly higher in the control group (unmatched population, 59 months vs. 38 months, p-value = 0.195; matched population, 53 months vs. 40 months, p-value = 0.797). In cox regression analysis, age < 60 years, advanced T stage, and presence of perineural invasion were independent factors for worse RFS, while tumor recurrence was an independent factor for poor OS. Patients with nonpancreatic PACA may have an OS benefit from adjuvant chemotherapy, and this needs to be validated with large prospective randomized studies.

Abstract CT137: Efficacy and immunological outcomes of non-fucosylated anti-CTLA-4 (BMS-986218) + degarelix acetate vs. degarelix acetate alone in men with high-risk localized prostate cancer (Neo-Red-P)

Abstract Background: Men with high-risk localized prostate cancer are at significant risk for disease recurrence and there is currently no role for neoadjuvant therapy. Although androgen deprivation therapy (ADT) is immunomodulatory and can increase CD8 T cell infiltration, these effects are counterbalanced by the expansion of suppressive regulatory T cells (Tregs). We therefore designed a correlative-rich clinical trial for men with high-risk localized prostate cancer to test whether BMS-986218 - a novel afucosylated anti-CTLA-4 antibody optimized for antibody-dependent cell-mediated cytotoxicity (ADCC) - depletes Tregs and augments response to ADT. Methods: Neo-Red-P is a single-center, two-arm, open-label pilot study assessing degarelix (ADT) versus ADT + anti-CTLA-4-NF (BMS-986218) in patients with treatment naïve high-risk localized prostate cancer. Key eligibility criteria included histologically confirmed adenocarcinoma with Gleason sum of ≥4+3 and clinical stage T1c-T3bN0M0. All patients received degarelix (ADT; 240mg SQ) 2 weeks before radical prostatectomy (RP). Patients were randomized to Arm A (ADT only), or Arm B (ADT + BMS-986218 [20mg IV] 2 doses Q2w starting 3 weeks before RP). The primary endpoint was the safety and feasibility of neoadjuvant BMS-986218 in prostate cancer. Secondary endpoints included the pathologic complete response rate, rate of undetectable PSA at 12 months, PSA response rate (&amp;gt;50% decrease pre-RP), and time-to-PSA recurrence. Fresh tumor specimens were collected at RP for single-cell RNA-sequencing, cytometry by time-of-flight, next-generation sequencing, and multiplex immunofluorescence. A treatment naïve cohort of matching demographic and pathological characteristics was collected for comparative analysis (n=14). Results: Between February 26, 2020, and November 15, 2022, 24 patients were enrolled. Severe treatment-related adverse events (TRAE; Grade ≥ 3) were rare in both arms; 0% in the ADT alone arm and 4% in the combination arm, suggesting a tolerable safety profile with the addition of BMS-986218. In the combination arm, 54% of subjects achieved a 50% reduction in PSA versus 33% in the ADT alone arm. In the ADT alone arm, 80% of patients had an undetectable PSA at 12 months, with a median recurrence-free survival of 1.61 years (IQR: 1.50-1.99 years). In the combination group, 75% had an undetectable PSA at 12 months, with a median recurrence-free survival of 1.82 years (IQR: 0.89-2.07 years). The overall recurrence rate in patients treated with combination therapy was 25% (3 of 12 patients) versus 20% (2 of 10 patients) in the ADT alone arm. Correlative studies suggest that aCTLA4-NF mitigates ADT-induced Treg accumulation through enhanced Fc receptor activity and augmented CTL activation, indicating an enhanced anti-tumor response with combination therapy. Conclusions: The neoadjuvant combination of ADT + aCTLA-4-NF (BMS-986218) is feasible, well tolerated, and induces significant remodeling of the immune TME through enhanced Fc receptor and CTL activity. Rates of disease recurrence following surgery were low in this high-risk population, warranting further investigation of combination immuno-hormonal therapy in the neoadjuvant setting for high-risk prostate cancer. Clinical Trial Information: NCT04301414 Citation Format: Patrick J. McCann, Casey R. Ager, Aleksandar Z. Obradovic, Matthew G. Chaimowitz, Samuel Pan, Caroline J. Laplaca, Parin Shah, Renu K. Virk, Christopher B. Anderson, Catherine S. Spina, Karie D. Runcie, Mark N. Stein, Charles G. Drake, Matthew C. Dallos. Efficacy and immunological outcomes of non-fucosylated anti-CTLA-4 (BMS-986218) + degarelix acetate vs. degarelix acetate alone in men with high-risk localized prostate cancer (Neo-Red-P) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT137.

Adjuvant Transarterial Chemoembolization With Sorafenib for Portal Vein Tumor Thrombus: A Randomized Clinical Trial.

Certain patients with hepatocellular carcinoma with portal vein tumor thrombus could benefit from surgical resection, and postoperative adjuvant therapy may lower the incidence of tumor recurrence. To compare the efficacy and safety of sorafenib plus transarterial chemoembolization vs sorafenib alone as postoperative adjuvant therapy for patients with hepatocellular carcinoma with portal vein tumor thrombus. This was a phase 3, multicenter, randomized clinical trial conducted in 5 hospitals in China. A total of 158 patients were enrolled and randomized from October 2019 to March 2022, with a median follow-up of 28.4 months. Portal vein tumor thrombus was graded by the Cheng classification. Eligible patients with hepatocellular carcinoma with Cheng grade I to III portal vein tumor thrombus (ie, involving segmental or sectoral branches, right- or left-side branch, or main trunk of portal vein) were included. Patients were randomly assigned 1:1 to receive transarterial chemoembolization with sorafenib or sorafenib alone as postoperative adjuvant therapy. Sorafenib treatment was started within 3 days after randomization, with an initial dose of 400 mg orally twice a day. In the transarterial chemoembolization with sorafenib group, transarterial chemoembolization was performed 1 day after the first administration of sorafenib. The primary end point was recurrence-free survival. Efficacy was assessed in the intention-to-treat population and safety was assessed in patients who received at least 1 dose of study treatment. Of 158 patients included, the median (IQR) age was 54 (43-61) years, and 140 (88.6%) patients were male. The median (IQR) recurrence-free survival was significantly longer in the transarterial chemoembolization with sorafenib group (16.8 [12.0-NA] vs 12.6 [7.8-18.1] months; hazard ratio [HR], 0.57; 95% CI, 0.39-0.83; P = .002). The median (IQR) overall survival was also significantly longer with transarterial chemoembolization with sorafenib than with sorafenib alone (30.4 [20.6-NA] vs 22.5 [15.4-NA] months; HR, 0.57; 95% CI, 0.36-0.91; P = .02). The most common grade 3/4 adverse event was hand-foot syndrome (23 of 79 patients in the transarterial chemoembolization with sorafenib group [29.1%] vs 24 of 79 patients in the sorafenib alone group [30.4%]). There were no treatment-related deaths in either group. The transarterial chemoembolization with sorafenib group did not show additional toxicity compared with the sorafenib monotherapy group. In this study, the combination of sorafenib and transarterial chemoembolization as postoperative adjuvant therapy in patients with hepatocellular carcinoma with portal vein tumor thrombus resulted in longer recurrence-free survival and overall survival than sorafenib alone and was well tolerated. ClinicalTrials.gov Identifier: NCT04143191.

Outcomes of Liver Resection and Transarterial Chemoembolization in Patients with Multinodular BCLC-A Hepatocellular Carcinoma.

This study aimed to compare the outcomes of liver resection (LR) and transarterial chemoembolization (TACE) in patients with multinodular hepatocellular carcinoma (HCC) within the Milan criteria who were not eligible for liver transplantation. We retrospectively analyzed 483 patients with multinodular HCC within the Milan criteria, who underwent either LR or TACE as an initial therapy between 2013 and 2022. The overall survival (OS) in the entire population and recurrence-free survival (RFS) in patients who underwent LR and TACE and achieved a complete response were analyzed. Propensity score (PS) matching analysis was also used for a fair comparison of outcomes between the two groups. Among the 483 patients, 107 (22.2%) and 376 (77.8%) underwent LR and TACE, respectively. The median size of the largest tumor was 2.0 cm, and 72.3% of the patients had two HCC lesions. The median OS and RFS were significantly longer in the LR group than in the TACE group (p <0.01 for both). In the multivariate analysis, TACE (adjusted hazard ratio [aHR], 1.81 and aHR, 2.41) and large tumor size (aHR, 1.43 and aHR, 1.44) were significantly associated with worse OS and RFS, respectively. The PS-matched analysis also demonstrated that the LR group had significantly longer OS and RFS than the TACE group (PS <0.05). In this study, LR showed better OS and RFS than TACE in patients with multinodular Barcelona Clinic Liver Cancer stage A HCC. Therefore, LR can be considered an effective treatment option for these patients.

Interferon-gamma signature as prognostic and predictive marker in macroscopic stage III melanoma

BackgroundA substantial proportion of patients with macroscopic stage III melanoma do not benefit sufficiently from adjuvant anti-PD-1 therapy, as they either recur despite therapy or would never have recurred. To...

301 Even Heterozygous Loss of CDKN2A B Greatly Accelerates Recurrence in Aggressive Meningioma

INTRODUCTION: In the WHO 2021 criteria, homozygous deletion of cyclin-dependent kinase-inhibitor 2A and/or B (CDKN2A/B) qualifies meningiomas as Grade 3. We assessed the effect of heterozygous CDKN2A/B loss, which was not addressed by the WHO, on recurrence-free survival (RFS), and evaluated the relationship of CDKN2A/B losses with our MenG classification. METHODS: Methylation and RNA-profiling were used to assign MenG. Methylation data identified heterozygous or homozygous loss of CDKN2A/B in 776 meningiomas. Clinical data for 659 tumors were used for survival analysis. RESULTS: Of the 776 tumors, 738 (95.1%) had intact CDKN2A/B, 20 (2.5%) had heterozygous loss of both CDKN2A/B, 3 (0.4%) had homozygous CDKN2A and heterozygous CDKN2B loss, and 15 (1.9%) had homozygous loss of both CDKN2A/B. Of the 659 tumors with clinical data, 28 (4.2%) showed any CDKN2A/B loss. RFS was based on concordant CDKN2A/B status. Tumors with intact CDKN2A/B (n = 631, mRFS not reached) had improved RFS compared to those with heterozygous loss (n = 15, mRFS = 29.1 mo) and homozygous loss (n = 11, mRFS = 10.5mo; p &lt; 0.0001 all groups, homozygous vs. heterozygous p = 0.4, Log-rank). Nearly all tumors with CDKN2A/B loss (27/28) were MenG C, the most aggressive group. Among MenG C tumors, presence of either homozygous (n = 11, mRFS 10.5mo) or heterozygous (n = 14, mRFS 25.1 mo) CDKN2A/B loss led to shortened RFS than those with intact CDKN2A/B (n = 198, mRFS 61.4 mo; p &lt; 0.0001 Log-rank). Median RFS was not reached in MenG A (n = 173) or MenG B (n = 259). Tumors with any CDKN2A/B loss had worse survival when controlling for WHO Grade (Grade: 2 p &lt; 0.0001, 3 p = 0.035, Log-rank). CONCLUSIONS: Heterozygous CDKN2A/B loss (not addressed in the 2021 WHO criteria) leads to poor outcome in meningioma even when controlling for molecular subgroup (MenG C) or WHO grade (2/3). All but 1 tumor (27/28) with any type of CDKN2A/B loss were MenG C.

Natural history of undifferentiated pleomorphic sarcoma: Experience from the US Sarcoma Collaborative.

Undifferentiated pleomorphic sarcoma (UPS) is a relatively rare but aggressive neoplasm. We sought to utilize a multi-institutional US cohort of sarcoma patients to examine predictors of survival and recurrence patterns after resection of UPS. From 2000 to 2016, patients with primary UPS undergoing curative-intent surgical resection at sevenacademic institutions were retrospectively reviewed. Epidemiologic and clinicopathologic factors were reviewed by site of origin. Overall survival (OS), recurrence-free survival (RFS), time-to-locoregional (TTLR),time-to-distant recurrence (TTDR), and patterns of recurrence were analyzed. Of the 534 UPS patients identified, 53% were female, with a median age of 60 and median tumor size of 8.5 cm. The median OS, RFS, TTLR, and TTDR for the entire cohort were 109, 49, 86, and 46 months, respectively. There were no differences in these survival outcomes between extremity and truncal UPS. Compared with truncal, extremity UPS were more commonly amenable to R0 resection (87% vs. 75%, p = 0.017) and less commonly associated with lymph node metastasis (1% vs. 6%, p = 0.031). R0 resection and radiation treatment, but not site of origin (extremity vs. trunk) were independent predictors of OS and RFS. TTLRrecurrence was shorter for UPS resected with a positive margin and for tumors not treated with radiation. For patients with resected extremity and truncal UPS, tumor size >5 cm and positive resection margin are associated with worse survival OS and RFS, irrespectively the site of origin. R0 surgical resection and radiation treatment may help improve these survival outcomes.

Recurrence and tumor-related death after resection of hepatocellular carcinoma in patients with metabolic syndrome

Background and aimsMetabolic syndrome (MS) is a growing epidemic and a risk factor for the development of hepatocellular carcinoma (HCC). This study aims to investigate the long-term outcomes of liver resection (LR) for HCC in patients with MS. Rates, timing, patterns, and treatment of recurrences were investigated, and cancer-specific survivals were assessed. MethodsBetween 2001 and 2021, data from 24 centers were collected. Overall survival (OS), recurrence-free survival (RFS), and cancer-specific survival were analyzed as well as recurrence patterns and treatment. The analysis was conducted using a competing-risk framework. The trajectory of the risk of recurrence over time was applied to a competing risk analysis. For post-recurrence survival, death due to tumor progression was the primary endpoint whereas deaths with recurrence due to other causes were considered as competing events. Results813 patients were included. Median OS was 81.4 months (28.1-157.0), and recurrence occurred in 48.3% of patients with a median RFS of 39.8 months (15.7-174.7). Cause-specific hazard of recurrence showed a first peak 6 months (0.027), and a second peak 24 months (0.021) after surgery. The later the recurrence, the higher the chance of receiving curative intent approaches (p=0.001). Size >5cm, multiple tumors, microvascular invasion, and cirrhosis were independent predictors of recurrence showing a cause-specific hazard over time. RFS was associated with death for recurrence (HR 0.985, 95%CI: 0.977, 0.995; p=0.002). ConclusionsPatients with MS undergoing LR for HCC have good long-term survival. Recurrence occurs in 48% of patients with a double peak incidence and time-specific hazards depending on tumor-related factors and underlying disease. The timing of recurrence significantly impacts survival. Surveillance after resection should be adjusted over time depending on risk factors.

The Risk of Metastatic Recurrence after Non-Curative Endoscopic Resection with Negative Deep Margins for Early Colorectal Cancer: Two-Center Retrospective Cohort Study

Introduction: Non-curative endoscopic resection of T1 colorectal cancer (CRC) carries a substantial risk of recurrence. However, previous studies have reported a significant proportion of cases in which the deep margin of endoscopic resection was positive for cancer due to the technical difficulties of colorectal endoscopic submucosal dissection (ESD). With the advancement of endoscopic technology and techniques resulting in the reduction of positive resection margins, it is important to reassess the long-term prognosis and major risk factors for recurrence in cases of negative deep margins. Methods: We conducted a retrospective cohort study of consecutive patients with T1 CRC who underwent endoscopic resection between January 2006 and December 2021 with negative deep margins. The histological findings of the resected specimens were analyzed to determine the risk factors associated with the primary outcomes of this study, including recurrence and cancer-related deaths. Results: The median age of the 190 patients was 70 years, of which 63% were male, and endoscopic treatment was performed in 64% by endoscopic mucosal resection and 36% by ESD. Eighty-two patients were in the curative resection (CR) group and 108 were in the non-curative resection (NCR) group, wherein the latter comprised 79 patients who underwent additional surgery (AS) and 29 patients who did not receive AS. Five-year recurrence-free survival rates were 98.4% (95% CI: 89.3–99.8) for CR, 98.3% (95% CI: 88.8–99.8) for NCR with AS, and 73.7% (95% CI: 46.5–88.5) for NCR without AS. Lymphatic invasion and budding grade 2/3 were the major risk factors for recurrence, with hazard ratios of 40.7 (p p = 0.007), respectively. Of the patients in the NCR group without AS, the 5-year recurrence-free rate was 85.6% (95% CI: 52.5–96.3) if there were no major risk factors (i.e., no lymphatic invasion or budding grade 2/3) (n = 21), whereas the prognosis was poor in the presence of one or more of the major risk factors, with a median recurrence-free survival and disease-specific survival of 2.5 and 3.1 years, respectively (n = 8). Discussion: In endoscopically resected T1 CRC with negative deep margins, lymphatic invasion or budding grade 2/3 may indicate a higher risk of recurrence when followed up without AS.

Abstract 7646: Evaluation of tumor immune microenvironment after neoadjuvant immunotherapy in patients with esophageal squamous cell carcinoma (ESCC): Towards a prediction for recurrence risk

Abstract Background: Despite the promising potential of neoadjuvant immune checkpoint blockade (ICB) in ESCC, postoperative recurrence remains a critical challenge. Besides pathological response, there remains no biomarkers for recurrence risk prediction after neoadjuvant ICB. Recent studies have highlighted a strong association between ICB efficacy and tumor immune microenvironment (TIME). Thus, we sought to investigate the TIME features in surgically resected tumors following neoadjuvant ICB from patients with ESCC to develop a potential way for recurrence risk prediction. Methods: This is a side study of a phase 2 NICE trial (ChiCTR1900026240) of 51 patients with resectable locally advanced ESCC who received neoadjuvant ICB plus chemotherapy followed by surgery from 2019 to 2020. TIME features of surgically resected tumors after neoadjuvant therapy were assessed by multiplex immunohistochemistry (mIHC) for immune markers (CD8, PD-L1, CD45RO, PD-1, Pan-CK, CD4, FoxP3, CD68, CD163). We first analyzed TIME features in tumors evaluated as pathological complete response (pCR) and major pathological response (MPR). Then, we divided 51 patients into a training and validation set; and machine learning was applied to identify a list of TIME features that predict recurrence-free survival (RFS) and to develop a TIME-based signature (TIS) on neoadjuvant ICB prognosis. Results: Fifty-one patients from NICE trial were used for primary analysis. A higher positive rate of CD8+ cells, CD163−CD68+ macrophages and CD8+CD45RO+ cells was observed in patients with pCR. Similarly, MPR patients exhibited a higher positive rate of CD8+ cells and CD8+CD45RO+ cells. Regarding RFS prediction, machine learning selection of TIS were identified: CD8+PD1−(cytotoxic T cells), CD4+Foxp3+ (Treg), CD8+CD45RO+ (memory T cells), and M1 macrophages (CD163−CD68+) exhibited significant predictive value. Stratifying patients into low- and high-risk groups using TIS for RFS revealed a prolonged prolonged RFS in the low-risk group (p&amp;lt;0.001; HR: 0.08, 95% CI [0.03-0.25]). Notably, when applying TIS to pCR patients, we identified a subset of high-risk pCR patients (median RFS = 8.9 months, 1- year RFS=32%) relapsed earlier than low-risk pCR patients (median RFS = not reached, 1-year RFS=100%, p&amp;lt;0.001). Multivariable Cox regression analysis demonstrated that TIS was an independent predictor for RFS as well as overall survival (both p&amp;lt;0.001). Further independent validation (ICB and non-ICB cohort) of TIS is ongoing. Conclusion: The establishment of a risk prediction model based on TIME demonstrated the potential to enhance postoperative monitoring management for ESCC patients who underwent surgery after neoadjuvant ICB. Our study provides insights into development of optimal post-immunotherapy management strategy. Citation Format: Zhichao Liu, Boyao Yu, Yuxin Yang, Cong Qi, Chang Yuan, Yang Yang, Jinzhi Wei, Sidong Chen, Yang Wang, Zhigang Li. Evaluation of tumor immune microenvironment after neoadjuvant immunotherapy in patients with esophageal squamous cell carcinoma (ESCC): Towards a prediction for recurrence risk [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 7646.

Abstract 6884: Evaluating tumor-infiltrating immune cells helps predicting prognosis in biliary tract cancer

Abstract Background: The tumor microenvironment (TME) is composed of not only cancer cells but also an extracellular matrix and many types of non-cancerous cells, including fibroblasts and immune cells. In recent years, infiltrating immune cells in TME are known as a predictor of chemotherapy and immunotherapy effectiveness. The purpose of this study is to evaluate infiltrations of lymphocytes and macrophages in biliary tract cancers (BTCs). Methods: Clinical data and tissues were obtained from 130 patients who underwent surgical treatment for BTCs (intrahepatic, perihilar, and distal bile duct cancer, gallbladder cancer, and ampullary cancer) at our institution between 2001 and 2017.The immunohistochemical evaluation was performed to evaluate the number of CD8+ T cells, CD4+ T cells and FOXP3+ T cells and CD68+ Macrophages around the tumor cells. We defined Immunoscore based on the status of infiltrating immune cells. With CD8-high, CD4-high, and FOXP3-high TILs and CD68-low TAMs as one factor, the number of factors was counted in each case, and Immunoscore was assigned a score of 5 stages, from 0 to 4. It was high for the score of 3-4 and low for the score of 0-2. Also, to evaluate the correlation with TME and systemic inflammatory reaction, we examined blood inflammatory biomarker from peripheral blood samples. Results: A total of 59 cases had high Immunoscore and 71 cases had low Immunoscore. Patients with high Immunoscore showed significantly superior overall survival (OS) and recurrence free survival (RFS) than those with low Immunoscore (median OS 60.8 vs. 26.4 months, p = 0.001; median RFS not reached vs. 17.2 months, p &amp;lt; 0.001). For OS, low Immunoscore, positive lymph node metastasis, presence of distant metastasis, and high serum CA19-9 level were independent poor prognostic factors (hazards ratio 2.05, 3.48, 1.7, and 2.05; p = 0.01, p = 0.005, p = 0.05, and p = 0.01, respectively). For RFS, low Immunoscore, T classification of pT3-4, and presence of distant metastasis were independent poor prognostic factors with hazards ratio of 2.41 (p = 0.001), 2.16 (p = 0.005), and 3.58 (p = 0.005), respectively. Patients with high preoperative Neutrophil-to-lymphocyte ratio (NLR) had a significantly lower average number of CD8+ T cells as compared to patients with low NLR (p = 0.02). Preoperative NLR was associated with infiltrating CD8+ T cells in TME. Conclusions: High Immunoscore group had significantly longer OS and RFS and was an independent good prognostic factor. Also, infiltrating CD8+ T cells in TME correlated preoperative NLR. Our findings indicated that in biliary tract cancer, the evaluation of infiltrating immune cells in TME was useful to predict patient prognosis, and preoperative NLR may predict the tumor infiltrating CD8+ T cells. Citation Format: Kousuke Hatta, Ryota Tanaka, Kenjiro Kimura, Shinpei Eguchi, Go Ohira, Hiroji Shinkawa, Kohei Nishio, Masahiko Kinoshita, Shigeaki Kurihara, Shuhei Kushiyama, Takahito Kawaguchi, Naoki Tani, Koichi Nakanishi, Mizuki Yoshida, Takeaki Ishizawa. Evaluating tumor-infiltrating immune cells helps predicting prognosis in biliary tract 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 6884.

Imaging and prognostic characterization of fat-containing hepatocellular carcinoma subtypes.

Steatohepatitic hepatocellular carcinoma (SH-HCC) is characterized by intratumoral fat with > 50% inflammatory changes. However, intratumoral fat (with or without inflammation) can also be found in not-otherwise specified HCC (NOS-HCC). We compared the imaging features and outcome of resected HCC containing fat on pathology including SH-HCC (> 50% steatohepatitic component), NOS-HCC with < 50% steatohepatitic component (SH-NOS-HCC), and fatty NOS-HCC (no steatohepatitic component). From September 2012 to June 2021, 94 patients underwent hepatic resection for fat-containing HCC on pathology. Imaging features and categories were assessed using LIRADS v2018. Fat quantification was performed on chemical-shift MRI. Recurrence-free and overall survival were estimated. Twenty-one patients (26%) had nonalcoholic steatohepatitis (NASH). The median intra-tumoral fat fraction was 8%, with differences between SH-HCC and SH-NOS-HCC (9.5% vs. 5% p = 0.03). There was no difference in major LI-RADS features between all groups; most tumors were classified as LR-4/5. A mosaic architecture on MRI was rare (7%) in SH-HCC, a fat in mass on CT was more frequently depicted (48%) in SH-HCC. A combination of NASH with no mosaic architecture on MRI or NASH with fat in mass on CT yielded excellent specificity for diagnosing SH-HCC (97.6% and 97.7%, respectively). The median recurrence-free and overall survival were 58 and 87months, with no difference between groups (p = 0.18 and p = 0.69). In patients with NASH, an SH-HCC may be suspected in L4/LR-5 observations with no mosaic architecture at MRI or with fat in mass on CT. Oncological outcomes appear similar between fat-containing HCC subtypes.

Outcome of adjuvant immunotherapy in a real-world nation-wide cohort of patients with melanoma

BackgroundClinical trials have demonstrated promising outcomes for adjuvant immunotherapy in patients with resected melanoma. Real-life data provide valuable insights to support patient guidance and treatment decisions. MethodsObservational population-based study examining a national cohort of patients with resected stage III-IV melanoma referred for adjuvant therapy. Data were extracted from the Danish Metastatic Melanoma Database (DAMMED). ResultsBetween November 2018 and January 2022, 785 patients received adjuvant anti-PD-1. The majority had stage III resected melanoma (87%), normal LDH levels (80%), and performance score 0 (87%). Patients were followed for a median of 25.6 months (95%CI 24−28). The median recurrence-free survival (RFS) and melanoma-specific survival (MSS) were not reached. The RFS was 78% (95%CI 75−81), 66% (63−70), and 59% (55−63); MSS was 97% (95−98), 93% (91−95), and 87% (84−90) at 1-, 2-, and 3-year; respectively. Less than half (42%) of the patients finalized planned therapy, 32% discontinued due to toxicity, and 19% due to melanoma recurrence. Patients discontinuing adjuvant treatment prematurely, without recurrence, had similar outcomes as patients finalizing therapy. In a multivariable analysis, ipilimumab plus nivolumab did not improve outcomes compared to ipilimumab monotherapy as a first-line metastatic treatment after adjuvant anti-PD-1. ConclusionSurvival outcomes in real-world patients with melanoma treated with adjuvant anti-PD-1 align with results from the randomized controlled trials. Patients discontinuing therapy prematurely, for other reasons than recurrence, had similar outcomes as patients finalizing planned treatment. First-line metastatic treatment with ipilimumab and nivolumab post-adjuvant anti-PD-1 did not show improved outcomes compared to ipilimumab/anti-PD-1 monotherapy.