Survival Outcomes In Patients Research Articles

Investigating survival outcomes in patients with early- vs late-onset colorectal cancer with liver metastases.

282 Background: Approximately 50% of patients with colorectal cancer develop liver metastases (CRLM). The incidence of early onset colorectal cancer (EOCRC), defined as <50 years of age at time of diagnosis, is increasing. In this study, we aim to explore the prognosis of early vs late onset colorectal cancer patients with CRLM who receive curative-intent treatment. Methods: A retrospective study was conducted to assess clinical outcomes in patients with CRLM presenting with EOCRC compared to those with late onset colorectal cancer (LOCRC). All patients underwent surgical resection and/or ablation between 2009 and 2024 at a tertiary care center. Groups were defined by patient age at the time of diagnosis of the primary tumor < 50 years versus ≥ 50 years. Demographics, tumor characteristics, and treatment modalities were compared between groups using Chi-square, independent samples t-test, and median test. Survival outcomes were assessed using Kaplan-Meier. Results: 342 patients met inclusion criteria. There were 85 (24.9%) EOCRC patients, with a median age at diagnosis of 44 years versus 63 years in the LOCRC group. EOCRC patients had fewer major medical comorbidities. EOCRC patients had a smaller proportion of right-sided (15.9% vs 29.6%, P=0.049) tumors. Rates of synchronous metastases (74.1% in EOCRC vs 72.4%, P=0.781), median size (28cm in EOCRC vs 25cm, P=0.421) median number of metastases (2 in EOCRC vs 2, P=0.385), and initial CEA levels (339.18 + 1276.48 ng/ml vs 328.87 + 2520.59 ng/ml, P=0.482) were similar between groups. However, EOCRC patients had higher rates of node-positive disease (75.6% vs 58.8%, P=0.010) and Fong Clinical Risk Scores 3-5 (57.0% vs 39.7%, P=0.009). Both groups underwent similar operative management with no differences in morbidity, but more EOCRC patients received neoadjuvant therapy (82.4% vs 66.1%, P=0.017). There were no significant differences in RAS/RAF (37.6% in EOCRC vs 34.2%, P=0.669) or TP53 (25.9% vs 34.6%, P=0.98) mutational status or microsatellite instability (stable in 74.1% in EOCRC vs 69.3%, P=0.523). Both intra- (46.5% in EOCRC vs 50.6%, P=0.535) and extra-hepatic (47.7% in EOCRC vs 38.1%, P=0.129) recurrences occurred at similar rates, with no significant differences in post-recurrence treatments received. Patients with CRLM and EOCRC had significantly worse overall survival, with a median time of 80 months versus 116 months (P=0.042). Conclusions: Despite similar clinical, pathologic, and genetic features, fewer medical comorbidities, and receiving similar medical and surgical treatments, EOCRC patients had worse median overall survival than LOCRC patients. High risk Fong Clinical Risk Scores were more common in the EOCRC group, who also received neoadjuvant therapy at higher rates. Additional research is needed to understand the differences in survival.

Definitive local therapy in solitary liver metastatic anal squamous cell carcinoma.

5 Background: Metastatic anal squamous cell carcinoma is rare and associated with a poor prognosis. There is limited evidence on the impact of local interventions on survival outcomes in patients with metastatic disease. We aimed to evaluate the survival of patients with liver-only metastatic anal cancer following definitive local management of liver lesions. Methods: This is a single-institution retrospective cohort study of patients with liver-limited metastatic anal cancer who underwent curative-intent local therapy. Clinical characteristics were collected and analyzed. The Kaplan-Meier method was used to calculate disease-free survival (DFS) and overall survival (OS). Prognostic factors associated with DFS and OS were assessed using Cox-proportional hazards models. Results: Twenty-five patients were included, median age was 59 years, and 92% were female. None of the patients had known HIV infection, 92% had HPV-positive disease and 76% had metachronous liver metastases following locoregional disease. All patients received chemoradiation for the primary lesion Unilobar hepatic involvement was present in 76% of the patients, with 56% having a single metastatic lesion. Pre-intervention systemic therapy was provided to 52% of the patients, including 8 who received carboplatin and paclitaxel, with a median duration of 3 months and ORR of 69%. Definitive treatment of metastatic disease included surgical resection (60%), non-surgical interventions (20%), and multimodal therapy (20%). All patients had viable tumor in the pathological specimen. With a median follow-up of 22 months, median DFS was 7.3 months, and median OS was 51.3 months. An ECOG performance status of 2, poorly differentiated histology, and extrahepatic recurrence were identified as significant prognostic factors in the univariate analysis, but not in the multivariate analysis. Conclusions: Our results demonstrate potential for long-term survival in liver-limited metastatic anal squamous cell carcinoma amenable to local therapeutic intervention combined with systemic therapy. These findings warrant further prospective study of local therapy in oligometastatic anal cancer. Characteristics N=25 (%) Median number of liver metastases (range), lesions- 1- 2-3- >3 1 (1-20)14 (56)8 (32)3 (12) Median maximal diameter of liver metastases (range), cm 3 (0.9-11.9) Best response of liver metastases to chemotherapy (N=13)- Complete response- Partial response- Stable disease- Progressive disease 2 (15)7 (54)3 (23)1 (8) Surgical procedure (N=20)- Right/left hemi-hepatectomy- Segmentectomy- Wedge resection 4 (20)14 (70)2 (10) Non-surgical procedure (N=10)- Local ablation- Radiotherapy- Other 5 (50)3 (30)2 (20) Hepatic surgical margins (N=20)- Positive margins- Close margins (<1mm)- Negative margins 02 (10)18 (90) Recurrent disease- Yeso Intrahepatico Extrahepatic- No 20 (80)14 (70)6 (30)5 (20)

Real-world evidence on genomic profiles and survival outcomes in patients with HER2-positive metastatic colorectal cancer.

58 Background: Patients (pts) with HER2-positive (HER2+) metastatic colorectal cancer (mCRC) represent a small, but increasingly important subgroup due to emerging HER2-targeted therapies. Although HER2 positivity is associated with resistance to anti-EGFR therapy (EGFRi), it is unclear if EGFRi or bevacizumab (BEV) is preferable as first-line (1L) therapy. Here, we offer novel evidence on the genomic profiles of pts with HER2+ mCRC and examine differences in survival between key treatment groups. Methods: This study used the US-based deidentified Flatiron Health-Foundation Medicine mCRC clinico-genomic database. The deidentified data originated from approximately 280 US cancer clinics (~800 sites of care). Included pts were 18 years or older, had evidence of stage IV or recurrent mCRC diagnosed between 01 Jan 2012 and 31 Mar 2022, and underwent tissue-based Comprehensive Genomic Profiling testing. HER2+ was defined as an ERBB2 copy number of ≥5 for diploid tumors. A doublet regimen was defined as fluoropyrimidines plus oxaliplatin or irinotecan. Data cut-off was 31 Mar 2024. Kaplan-Meier methods were used to examine real-world overall survival (rwOS) and progression-free survival (rwPFS) overall, by 1L treatment class and across key subgroups defined by tumor sidedness and genomic profile, indexed to the start of 1L with pts censored at their last EHR-recorded activity. Results: Among a cohort of 5545 pts, HER2+ was detected in 171 (3.1%) pts. Median age (years) was 57 for HER2+ vs 61 for HER2-; 69.3% of HER2+ pts were White, compared to 72.1% in HER2-. Among pts with HER2+, 31 (18.1%) had RAS mutation (mt), BRAF V600E mt, or microsatellite instability-high. ERBB2 copy number was significantly lower in pts with RAS mt or BRAF V600E mt compared to those without these mutations (p < 0.01, p = 0.045, respectively). Among pts who received 1L treatment (n=4748), rwPFS significantly differed between HER2+ (n=144) and HER2-negative (HER2-; n=4604) groups (7.6 vs 8.7 months, unadjusted HR (uHR) 1.20, p=0.04). This difference was consistent in pts with left-sided RAS/BRAF V600E wild-type microsatellite stable (MSS) mCRC and treated with 1L doublet plus EGFRi (8.7 vs 12.5 months, uHR 2.18, p=0.02; n=10 HER2+,n=117 HER2-) or 1L doublet plus BEV (8.9 vs 10.5 months, uHR 1.65, p=0.04; n=20 HER2+, n=387 HER2-). No significant rwPFS difference was observed between EGFRi and BEV in the HER2+ subgroup. rwOS showed no significant difference between HER2+ and HER2- groups (overall: 26.1 vs 24.5 months, uHR 0.94, p=0.52; n=144 HER2+, n=4604 HER2-). Conclusions: Although about 80% of pts with HER2-positive mCRC are RAS/BRAF V600E wild-type and eligible for EGFRi, no survival benefit was observed in EGFRi relative to BEV as first-line combination. While the impact of potential confounders needs to be examined in further analyses, these findings highlight the need for specific treatments for pts with HER2+ mCRC.

Incidence and survival trends in small bowel adenocarcinoma (SBA) from 2000-2019 in the United States.

801 Background: SBA is a rare, poorly understood gastrointestinal malignancy. Adenocarcinomas are often grouped with other small bowel cancer histologies in epidemiologic and outcomes reports, which limits the ability to detect SBA-specific trends. Recent studies in European populations show increasing SBA incidence, but there are limited published data in American cohorts. Identifying trends in SBA can improve understanding of the population most at risk for developing SBA. This study describes U.S. trends in SBA incidence and outcomes from 2000 to 2019. Methods: Using the 2022 SEER research-limited dataset, we identified SBA cases and measured the incidence change from 2000-2019. We built linear regression models to evaluate changes in annual incidence by groups, including sex, race, and age of diagnosis, separately. We then compared the overall incidence and trends between subgroups. We investigated overall survival (OS) through the SEER research case listings for SBA patients diagnosed during the study period. Results: An average of 0.67 cases/100,000 SBA cases were reported annually from 2000-2019, with a median diagnosis age of 69 years. SBA incidence has increased annually by 0.3% per year from 2000-2019 (p=0.05). From 2000-2019, men were at a higher risk for SBA compared to women (p=0.02). In men, SBA cases increased at a rate of 0.004 cases/100,000/year from 2000-2019 (p=0.01) and a nonsignificant decrease in women of 0.00012 cases/100,000/year. There were no statistically significant differences in incidence or the change in incidence of SBA by race. The age-adjusted incidence was significantly higher each year between 2000 and 2019 in the > 70 cohort compared to the <70 cohort (p=0.02). Cases of SBA increased at a rate of 0.02 cases/100,000/year in adults >70 years (p=0.02). There were no differences in incidence rates in patients <70 years. There was no significant difference in OS for patients diagnosed with SBA in 2000, 2005, 2010, 2015, and 2019 (p=0.21). Conclusions: The overall annual incidence of SBA is increasing in the U.S. population. The most significant rate increases are in men and adults older than 70. In the SEER population, trends in SBA contrast with the recent rise of colorectal cancer in the young adult population, highlighting the unique nature of SBA compared to other gastrointestinal malignancies. Additionally, survival outcomes in patients diagnosed with SBA have remained stable over the past 20 years, while other malignancies have shown improvement in the same period. The small cohort size and the lack of a universal U.S. cancer registry limited this evaluation. Improved reporting of SBA cases and further research to identify risk factors are urgently needed to reduce the growing impact of SBA.

The effect of renin-angiotensin system inhibitors on patients with pancreatic cancer receiving systemic treatment: A retrospective cohort study from TriNetX US collaborative networks.

734 Background: This study aimed to assess the impact of renin-angiotensin system inhibitors, including angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs), on patients with pancreatic cancer undergoing systemic chemotherapy. Methods: We conducted a global, retrospective collaborative network analysis using TriNetX data from January 1, 2014, to December 31, 2023, to explore this question. The study captured data on pancreatic cancer diagnoses, comorbidities, medications, and survival outcomes. Propensity score matching (PSM) was used to create 1:1 matched groups. Hazard ratios (HR) with 95% confidence intervals (95% CI) were calculated to assess survival outcomes, while the Kaplan–Meier method was employed to evaluate survival probabilities. Subgroup analyses were performed based on sex, age, surgery, race, and comorbidities. Results: The study included 1,861 patients who were on ARBs/ACEIs and 4,875 patients who were not on these medications at baseline. After 1:1 propensity score matching, both groups were well-balanced with 1,627 patients each. Compared to the non-ARBs/ACEIs group, patients receiving ARBs/ACEIs demonstrated significantly better overall survival (HR: 0.846, 95% CI: 0.753–0.949). Subgroup analyses revealed significantly improved survival outcomes in patients on ARBs/ACEIs, including those without surgery (HR: 0.846, 95% CI: 0.749–0.956), males (HR: 0.762, 95% CI: 0.640–0.908), patients aged 65 years and older (HR: 0.801, 95% CI: 0.709–0.906), and White patients (HR: 0.806, 95% CI: 0.704–0.924). Notably, similar survival benefits were observed in patients with comorbidities such as diabetes, ischemic heart disease, dyslipidemia, and hypertension. Conclusions: In the largest TriNetX matched cohort study on pancreatic cancer, the use of ARBs/ACEIs was associated with a reduced risk of overall mortality. However, prospective studies are needed to further evaluate the effects of concomitant ARB/ACEI use in patients with pancreatic cancer undergoing systemic treatment.

Analysis of lipogenic and metabolic subtypes and survival outcome in patients with pancreatic adenocarcinoma.

775 Background: Delayed diagnosis and rapid progression are major drivers of poor survival outcomes for Pancreatic Ductal Adenocarcinoma (PDAC). In previous studies, molecular profiling in tumor tissue has identified Cholesterogenic, Classical, or Exocrine-Like pathological subtypes associated with improved prognosis. Herein, in a clinical trial called Project Survival, we molecularly and clinically characterized a prospective PDAC biomarker cohort. This multicenter (n=6) clinical trial (NCT 02781012) of PDAC combined with high-fidelity longitudinal phenotypic characterization and multi-omic profiling was utilized to identify biomarkers with diagnostic and therapeutic utility. The study included assessment of plasma, serum, buffy coat, urine, saliva, and tumor tissue samples and followed 269 PDAC subjects for up to 7 years (Median survival was 700 days, with IQR of 822 days). Methods: We assessed plasma samples to identify circulating biomarkers using proteomics, metabolomics, and lipidomics profiling. Multi-omic comparison of patients with Overall Survival (OS) above the 75th percentile (improved survival) against those with OS below the 25th percentile (poor survival) was performed. Results: We identified distinct panels of proteins, metabolites, and lipids that were associated with patient survival outcomes. Protein biomarkers that were increased in improved survival outcomes were associated with cholesterol metabolism (7/14, p-value = 0.00085) and glycolysis/gluconeogenesis (5/12, p-value = 0.00089), however, protein markers associated with immune surveillance and inflammation were associated with poorer survival. For metabolite biomarkers, 19 metabolites were increased in poorer survivors of which 13/19 were carnitine metabolites, and 42 metabolites were increased in patients with improved survival. Interestingly, only two lipid molecular species of the diacylglyceride family were increased in patients with poorer survival. Conclusions: Project Survival, a prospective biomarker-driven clinical trial identified distinct metabolic and molecular subtypes of patients which characterize survival outcome in PDAC. These subtypes go beyond tumor genomic characterization and align with distinct cholesterogenic and glucogenic phenotypes associated with survival outcomes, which can potentially be leveraged for therapeutic intervention strategies.

The prognostic significance of sarcopenia in patients treated with definitive radiotherapy: A systematic review.

Sarcopenia describes the degenerative loss of muscle mass and strength, and is emerging as a pan-cancer prognostic biomarker. It is linked with increased treatment toxicity, decreased survival and significant healthcare financial burden. Systematic analyses of sarcopenia studies have focused on outcomes in patients treated surgically or with systemic therapies. There are few publications concerning patients treated with radiotherapy. This manuscript presents a pan-cancer systematic review of the association between sarcopenia and survival outcomes in patients treated with definitive (chemo-)radiotherapy. A literature search was performed, with 26 studies identified, including a total of 5,784 patients. The prognostic significance of sarcopenia was mixed. This may reflect lack of consensus in methods used to measure skeletal muscle mass and define sarcopenia. Many papers analyse small samples and present sarcopenia cutoffs optimised on the local population, which may not generalise to external populations. Recent advances in artificial intelligence allow for automatic measurement of body composition by segmenting the muscle compartment on routinely collected imaging. This provides opportunity for standardisation of measurement methods and definitions across populations. Adopting sarcopenia diagnosis into clinical workflows could reduce futile treatments and associated financial burden, by reducing treatment toxicities, and improving treatment completion, patient survival, and quality-of-life after cancer.

Retrospective comparative survival analysis of ablation plus systemic therapy versus systemic therapy alone for breast cancer liver metastases, stratified by extrahepatic metastases status.

Current decision-making for the treatment of breast cancer liver metastases (BCLM) using ablation lacks strong evidence, especially for patients combined with extrahepatic metastases. To assess whether ablation plus systemic therapy (AS) improves survival outcomes in patients with BCLM compared to systemic therapy alone. This retrospective study analyzed patients with BCLM who received either AS or systemic therapy alone. Propensity score matching (PSM) and survival analysis were performed, taking into account factors like the characteristics of primary breast cancer, liver metastases and systemic therapies received. The study included 1021 female patients, with a median follow-up of 39.6 months. Of these patients, 132 underwent AS and 836 received systemic therapy alone. After PSM, among patients with BCLM (≤3 tumors, each ≤3cm), the median overall survival (OS) for those treated with AS or systemic therapy alone was 65.5 and 40.4 months, respectively (HR=0.48, p=.003); in the subset of patients with extrahepatic metastases, the median OS for those treated with AS and systemic therapy alone was 46.4 and 40.8 months, respectively (HR=0.58, p=.047). Among patients with >3cm or >3 lesions, the median OS for those treated with AS or systemic therapy alone was 45.2 and 29 months, respectively (HR=0.67, p=.084). Among patients with BCLM (≤3 tumors, each ≤3cm), AS provide longer survival compared to systemic therapy alone, even with extrahepatic metastases. For patients with larger or more numerous metastases (>3cm or >3 lesions), AS may provide survival benefit, but further validation is needed.

Investigation of the association of CTRB2 exon 6 deletion with time to progression and overall survival in pancreatic ductal adenocarcinoma.

770 Background: Pancreatic ductal adenocarcinoma (PDAC) is associated with poor prognosis and limited treatment options. A 584 bp deletion in CTRB2 , which impairs chymotrypsin B2 function, has been linked to increased PDAC risk. This study investigates the impact of this deletion on progression and survival outcomes in patients with PDAC. Methods: There were 633 patients in whom CTRB2ex6 deletion was genotyped; 263 patients received chemotherapy and had time to progression (TTP) information. TTP was calculated from diagnosis date until earliest of 1) progression date (event), 2) surgery, death, or next chemotherapy date (competing risk), or 3) date last known to be alive (censor). Overall survival (OS) was calculated for the cohort from diagnosis until date of death (event) or date last known to be alive (censor). TTP was analyzed using cumulative incidence methods accounting for competing risks; OS was analyzed using Kaplan-Meier methods. Cox proportional hazard models adjusted for age and sex were used to test associations and compute hazard ratios (HR) and 95% confidence intervals (CI). Results: Median TTP in those with CTRB2ex6 deletion negative carrier status (n=209) was 1.3 years vs 5.9 years for those with positive carrier status (n=54). Estimated 3-year progression rates were 54.2% for patients with no CTRB2ex6 deletions, 43.7% for patients with one deletion (n=48), and 33.3% for patients with two CTRB2ex6 deletions (n=6). TTP was not associated with CTRB2 deletion carrier status (HR: 0.8, 95% CI: 0.6-1.3). Median OS for CTRB2ex6 deletion negative carriers (n=514) was 1.0 year vs 0.9 years for positive carriers (n=119); within deletion carriers, heterozygous carriers (n=110) had a median OS of 0.9 years, and homozygous carriers (n=9) had a median OS of 2.6 years. OS was not associated with CTRB2 deletion carrier status (HR: 1.0, 95% CI: 0.9-1.3). Conclusions: Although we did not detect statistically significant differences in TTP and OS by CTRB2ex6 deletion carrier status, there was an interesting trend toward longer TTP and OS in the small number of patients who carried homozygous CTRB2ex6 deletions. Larger studies are warranted to validate these findings.

Sex differences in toxicities and survival outcomes among patients with stage III colorectal cancer receiving adjuvant fluoropyrimidine monotherapy: A pooled analysis of four randomized controlled trials (JCOG2310A).

116 Background: Fluoropyrimidine agents are the key component of adjuvant chemotherapy for pathological stage III colorectal cancer (CRC). Western studies have shown that female sex is associated with favorable survival outcomes after surgery, yet a risk factor for fluoropyrimidine-related adverse events (AEs) during adjuvant chemotherapy. However, it remains unclear whether there are sex differences in the treatment outcomes in this setting among the Japanese population. Methods: Patients enrolled in four randomized controlled trials (JCOG0205, JCOG0404, JCOG0910, and JCOG1006) who received adjuvant fluoropyrimidine monotherapy for pathological stage III CRC were analyzed. Incidences of AEs and survival outcomes (relapse-free survival [RFS], and overall survival [OS]) were compared between males and females. Multivariable logistic regression analyses were performed to evaluate associations between sex and the development of AEs. Multivariable Cox regression analyses were performed using Cox proportional hazard models to evaluate associations between sex and survival outcomes. Results: A total of 3170 patients (male, n = 1654; female, n = 1516) were included in the analysis. Compared with male patients, female patients were more likely to require dose reduction (male, 20.4%; female: 28.8%, p < 0.0001) and had low completion proportions of adjuvant chemotherapy (male, 81.7%; female, 77.0%, p = 0.0011). Female patients experienced higher incidences of any-grade hematological and non-hematological AEs (Table). Female sex was associated with higher incidences of grade 3/4 hematological AEs (odds ratio [OR]: 1.702 [95% CI 1.272–2.278], p = 0.0003) and non-hematological AEs (OR: 1.666 [95% CI 1.373–2.020], p < 0.0001). Female sex was identified as a favorable prognostic factor for RFS (hazard ratio [HR]: 0.729 [0.627–0.848], p < 0.0001) and OS (HR: 0.796 [0.653–0.970], p = 0.0238). Conclusions: Sex differences had implications for the development of AEs and survival outcomes of Japanese patients with pathological stage III CRC who received adjuvant fluoropyrimidine monotherapy. Incidences of adverse events. Adverse event Any grade Grade 3/4 Male% (95% CI) Female% (95% CI) p-value Male% (95% CI) Female% (95% CI) p-value Any hematological toxicity 63.7 (61.3–66.0) 83.9 (82.0–85.8) <0.0001 5.0 (4.0–6.1) 8.9 (7.5–10.4) <0.0001 Any non-hematological toxicity 93.3 (92.0–94.5) 96.1 (95.0–97.0) 0.0006 13.3 (11.7–15.1) 20.8 (18.8–22.9) <0.0001

Perioperative chemotherapy with either S-1 or 5-fluorouracil plus oxaliplatin and docetaxel for locally advanced gastric or gastroesophageal junction adenocarcinoma: A prospective trial and matched comparison.

396 Background: Perioperative triplet chemotherapy improves the survival and surgical outcome of patients with locally advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma in addition to curative surgery. 5-fluorouracil (5-FU), docetaxel, oxaliplatin and leukovorin (FLOT) has been suggested as the treatment of choice. S-1, an oral fluoropyrimidine chemotherapeutic, also shows compelling efficacy as one of the triplet backbone and is exempt from a prolonged infusion time. However, a comparison over efficacy and tolerability between S-1 or 5-FU-containing triplet has not been investigated. Methods: The study contains two parts. The first part was a prospective single-arm multi-centered phase II trial with eight cycles of perioperative leucovorin, oxaliplatin, docetaxel and S-1 (LOTS) in patients with ≥T3 any N or ≥T2N(+) non-metastatic gastric/GEJ adenocarcinoma. The primary endpoint was the treatment response assessed by pathological tumor regression (TRG). After confirming the result passing the statistical threshold, we compared them with an identical and independent patient population who received perioperative FLOT under a prospective observation. A propensity score matching (PPSM) was used to balance the heterogeneity between the two groups. The efficacy, survival and tolerability were compared in a post-hoc manner. Results: From Feb 2017 to Jan 2024 with a comparable median follow-up time (LOTS, 18.7 ms; FLOT, 18.9 ms), a total of 45 and 154 patients were enrolled and received either LOTS or FLOT treatment. After a one-to-two PPSM procedure, the baseline characteristics of patients were comparable (LOTS, n=45; FLOT, n=90). Patients had similar curative resection rates (LOTS, 91%; FLOT, 86%; p=.359) and above nearly complete pathological regression rates (TRG 0-1: LOTS, 23%; FLOT, 27%; p=.669). The 24-ms recurrence-free (RFS) and overall survival (OS) rates were also comparable (LOTS vs. FLOT: 66 vs. 59% in RFS, p=.463; 73 vs. 68% in OS, p=.491). The toxicities were tolerable, except that more diarrhea and nausea events were reported in the LOTS group, whereas neutropenia, thrombocytopenia and mucositis were significantly prominent in the FLOT group. Conclusions: Perioperative LOTS shows reasonable therapeutic efficacy and survival as compared with FLOT in patients with locally advanced gastric/GEJ cancer. While the toxicity profile is distinctive from FLOT, it could be a potential alternative regimen with the convenience to save the prolonged infusion time. Clinical trial information: NCT04999332 . Pathological outcome. Prior to LOTS treatment (n=45) After LOTS treatment (n=43) Prior to FLOT treatment (n=90) After FLOT treatment (n=86) p in LOTS vs. FLOT CAP TRG, n (%) 0.669 0 - - 1 (2.3) - - 3 (3.5) 1 - - 9 (20.9) - - 20 (23.3) 2 - - 14 (32.6) - - 23 (26.7) 3 - - 19 (44.2) - - 40 (46.5)

Optimal preoperative treatment strategy for conversion surgery in unresectable locally advanced pancreatic cancer: A project study by the Japanese Society of Hepato-Biliary-Pancreatic Surgery.

718 Background: Conversion surgery (CS) for unresectable locally advanced pancreatic cancer (UR-LAPC) has been widely accepted when feasible. However, optimal preoperative treatment strategies remain unclear. To determine the most effective preoperative approach for UR-LAPC in the current treatment landscape, we conducted a project study in the Japanese Society of Hepato-Biliary-Pancreatic Surgery. Methods: We analyzed 465 UR-LAPC patients who underwent CS following chemotherapy with FOLFIRINOX (FFX), gemcitabine plus nab-paclitaxel (GnP), or modified regimens between 2015 and 2020 across 84 Japanese board-certified training institutions. Overall survival (OS) was the primary endpoint. We used the Kaplan-Meier method for estimating survival analyses, the Cox proportional hazards model for multivariate analyses, and Maximally Selected Rank Statistics to determine the optimal preoperative treatment duration. Results: Median OS was 43.8 months, with a 5-year survival rate of 37.2%. The optimal preoperative treatment duration was 6.1 months. Patients receiving >6 months of preoperative treatment (n=350) showed significantly better median OS and recurrence-free survival (RFS) compared to ≤6 months (n=115) (50.4 vs 29.7 months and 15.6 vs 9.1 months, respectively; both P<0.001 ). FFX-based regimens (n=116) showed better OS and RFS than GnP-based regimens (n=349) (65.0 vs 36.5 months and 19.3 vs 12.4 months, respectively; both P<0.01 ). Multivariate analysis identified preoperative treatment >6 months (HR 0.53, 95% CI 0.407-0.697, P<0.001 ) and initial FFX-based regimens (HR 0.63, 95% CI 0.464-0.843, P=0.002 ) as independent prognostic factors. Additional favorable factors included normal CA19-9 and CEA levels, PNI>45 before CS, adjuvant chemotherapy, R0 resection, and Evans grade III/IV. Conclusions: This large-scale retrospective study has demonstrated that preoperative treatment duration >6 months and the use of FFX-based regimens as initial treatment were associated with improved survival outcomes in UR-LAPC patients undergoing CS. These findings provide critical information for considering CS in UR-LAPC patients, especially in current clinical practice.

Prevalence and Clinical Outcomes of Human Epidermal Growth Factor Receptor 2 Expression in Patients With Advanced Urothelial Carcinoma.

The prognosis for urothelial carcinoma remains poor, with limited therapeutic options, emphasizing the need for further research into targeted therapies. The prognostic and predictive significance of human epidermal growth factor receptor 2 (HER2) expression in urothelial carcinoma remains unclear, with previous studies reporting conflicting results. We conducted a retrospective analysis of advanced urothelial carcinoma cases diagnosed between January 2017 and December 2022. HER2 status was prospectively determined using the Leica CB11 antibody on available biopsy specimens. Patient data, tumor characteristics, and survival outcomes were retrieved from hospital records for analysis. Of the 84 patients initially identified with muscle-invasive disease, HER2 immunohistochemistry (IHC) was performed on 50 samples. Among these, 54% exhibited HER2 scores ≥ 1+, with 22% classified as HER2-positive (3+ score by IHC), 10% as equivocal (2+ score by IHC), and 22% as HER2-low (1+ score by IHC). The distribution of HER2 score ≥ 1+ tumors included 25.7% in the bladder, 20.0% in the renal pelvis, and none in the ureter. HER2-positive (3+ score by IHC) tumors were all histological grade 3. Among these patients, 13.4% presented with localized disease, 20% with locally advanced disease, and 50% with metastatic disease at the time of diagnosis. Notably, 42.8% of recurrent tumors originating from the renal pelvis and 62.5% of those from the bladder exhibited HER2 scores ≥ 1+. Among patients diagnosed with non-metastatic disease, 100% with renal pelvis tumors and 75% with bladder tumors experienced metastatic recurrence if they were HER2-positive (3+ score by IHC). The overall survival for HER2-negative patients was 31.0 months (95% confidence interval (CI): 15.29 - 66.70) compared to 13.0 months (95% CI: 7.32 - 18.68) in the HER2 score ≥ 1+ population (P = 0.0029). In this cohort of Mexican patients with urothelial carcinoma, HER2 expression was observed in 54.4% of cases. HER2-positive (+3 by IHC) tumors were associated with higher histological grade and worse prognostic outcomes, including increased recurrence, progression, and mortality.

WW vs TME in patients with rectal cancer with a complete or near-complete response to TNT: Pooled analysis of CAO/ARO/AIO-12 and OPRA trials.

21 Background: Patients with locally advanced rectal cancer (LARC) and a clinical complete response (cCR) or near-complete response (nCR) to total neoadjuvant therapy (TNT) can be offered watch-and-wait (WW) with the intention of achieving organ preservation. However, one third of patients on WW develop tumor regrowth and require total mesorectal excision (TME). Assessing the safety of WW in patients with a cCR or nCR is challenging due to the difficulty of finding an adequate control group. Here we compare the survival outcomes of patients with LARC treated with TNT and either mandatory TME or selective WW stratified by tumor response. Methods: This is a pooled analysis of two multicenter, phase II trials (CAO/ARO/AIO-12 [CAO] and OPRA) that randomized patients with stage II/III rectal cancer to either induction or consolidation TNT. All patients in the CAO trial underwent TME within 6 weeks of TNT. Pathologic tumor regression grade (TRG) was categorized as complete (TRG 4), intermediate (TRG 2,3) or poor (TRG 0,1). Patients in the OPRA trial were restaged by endoscopy and MRI 8±4 weeks after end of TNT. Clinical response was graded as cCR, nCR, or incomplete clinical response (iCR). Patients with a cCR or nCR were offered WW; patients with an iCR were recommended for TME. Survival curves were estimated using the Kaplan-Meier method and the log-rank test. Results: The study included 628 patients ( n =304 CAO; n =324 OPRA). Median follow-up was 3.6 (IQR 1.13) and 5.1 (IQR 2.2) years. Patients in the CAO trial were more likely to have cT3/4 and cN positive disease while patients in the OPRA trial had tumors closer to the anal verge. Compliance with TNT and rates of grade 3+ adverse events were similar between studies. A total of 144 (47%) patients in the OPRA trial achieved long term organ preservation. We found no differences in survival between trials. In addition, we found no differences in DFS between studies for patients with an excellent (TRG4 87% [95% CI, 79-97%], cCR 87% [95% CI, 81-93%]) or intermediate (TRG2-3 69% [95% CI, 62-76%], nCR 71% [95% CI, 68-80%]) response. Conclusions: This pooled analysis demonstrated that almost half of LARC patients treated with TNT can achieve organ preservation and that a selective WW strategy yields similar survival outcomes compared to mandatory TME. In addition, we found no differences in survival based on paired clinical and pathologic tumor response grades following TNT. This data provides further evidence supporting the safety of WW for patients with LARC and a cCR or nCR to TNT. Three-year survival outcomes in the CAO/ARO/AIO-12 and OPRA trials. CAO/ARO/AIO-12(95% CI) OPRA(95% CI) P 3y DFS 73 (71–81)% 76 (68–78)% 0.3 3y DRFS 82 (78–87)% 82 (78–87)% 0.7 3y LRFS 95 (92–98)% 95 (92–97)% 0.4 3y OS 92 (89–95)% 94 (89–95)% 0.5 DFS: disease-free survival, DRFS: distant recurrence-free survival, LRFS: local recurrence-free survival, OS: overall survival.

Chemoimmunotherapy plus radiotherapy in advanced esophageal squamous-cell carcinoma.

437 Background: Chemotherapy plus Immune checkpoint inhibitors (ICIs) have improved survival outcomes of patients with advanced or metastatic esophageal squamous-cell carcinoma in both first- and second-line settings. However, the benefit of additional radiotherapy for the residual esophageal lesion after chemo-immunotherapy remains unclear. Methods: We conducted a one-arm, three-center, open label study involving patients who were treatment naïve, radiological and histological confirmed advanced or metastatic squamous-cell esophageal carcinoma. Enrolled patients were expected the survival time was three months or longer; and ECOG performance status score was 0 or 1. In induction phase, patients received four cycles of TP regimen chemotherapy (docetaxel, 75/mg 2 , iv on day 1 and cisplatin, 75mg/m 2 , iv on day 1) combined with PD-1 inhibitor (sintilimab, 200mg intravenous infusion on day 1) every 21 days. Patients who finished four cycles of chemo-immunotherapy with stable disease (SD) or partial response (PR) were initiated 50Gy/25f irradiation for residual tumors. 3-4weeks after radiotherapy, maintenance sintilimab therapy was administered every 21 days for another 31 cycles or until disease progression or intolerable toxicity. Results: Total of 39 patients were enrolled in this study, 30 of them could be evaluated in efficiency and toxicities. All of them were male and were squamous-cell carcinoma in histology. 12/30 (40.0%) patients were in stage III, and 18/30 (60.0%) were in stage IV. 29/30 (96.7%) patients completed four cycles chemo-immunotherapy, the complete response (CR) rate was 6.7% (2/30), the partial response (PR) rate was 53.3% (16/30) and disease control rate (DCR) was 86.7% (26/30). The median depth of response (DpR) was 34.5% for chemoimmunotherapy and was 64.0% after radiotherapy. The progression-free survival (PFS) was 16.4 months and the overall survival (OS) was not reached. The most common grade 3 or worse adverse event was neutropenia and occurred in 3 (10.0%) patients. Conclusions: Four cycles sintilimab plus cisplatin and docetaxel followed by radiotherapy for residual tumors and maintained sintilimab had high response rate, prolonged PFS and tolerable toxicities as first line treatment in patients with advanced or metastatic esophageal squamous-cell carcinoma. Longer OS is promising and more patients enrolled in this study is needed in future. Clinical trial information: NCT06138028 . Clinicopathological features and patient factors. Factors No. of patients (n=30) (%) Gender Male 30 (100.0) Female 0 (0) Age (year) < 65 27 (43.3) ≥ 65 17 (56.7) PD-L1 (CPS) < 5 9 (30.0) ≥ 5 21 (70.0) Clinical Stage III 12 (40.0) IV 18 (60.0) Metastatic Pattern Regional lymph node 12 (40.0) Cervical & Supraclavicular 4 (13.3) Abdomen 5 (16.7) Lung 6 (20.0)

Comparative outcomes of neuroendocrine tumors in the historically underserved population of Bronx, NY: Montefiore Einstein Comprehensive Cancer Center.

671 Background: Neuroendocrine tumors (NETs) pose different clinical implications based upon age at diagnosis, with regards to early-onset (EO<50yrs) versus late-onset (LO>=50yrs) disease. While primary-tumor resection is crucial for localized NETs, its benefit in metastatic cases without metastasectomy remains uncertain. This study examines variables associated with survival in EO versus LO cases, including primary tumor resection. Methods: A retrospective cohort of 91 patients with gastrointestinal(GI)-NETs were identified as part of an IRB-approved project. Disease-stage (local vs. metastatic), tumor grade (G1-3), 5-year-survival, primary-tumor removal, and race/ethnicity were included in this analysis. Results: Among all patients, 31.9% identified as Hispanic, 33% as non-Hispanic Black, 22% as non-Hispanic White, and 13.1% as other. Among all patients, 79 were classified as G1/G2. Among LO patients, 87.5% (n=63) were G1/G2, among which 46% (n=29) were metastatic. Among EO patients, 84% (n=16) were G1/G2, among which 68.8% (n=11) were metastatic. In the LO group with G1/G2 tumors, 5-year survival rate was 48.3% for metastatic disease and 58.8% for localized disease. For EO with G1/G2 tumors, the 5-year survival rate was 72.7% for metastatic disease and 80% for localized disease. In the EO G1/G2 group, 5 of the 11 patients with metastatic disease had primary tumor removal without metastasectomy with 100% 5-year survival rate. In the LO G1/G2 group, 7 of 29 metastatic patients had primary tumor removal without metastasectomy, with 86% 5-year survival rate. Resection of primary tumor (without metastasectomy) in patients with metastatic G1/G2 NETs was associated with improved 5-year survival, independent of age at diagnosis ( p-value =0.008), as shown in the table. Conclusions: This study helps to emphasize the importance of primary tumor removal in improving survival outcomes for patients with metastatic low-grade GI-NETs, regardless of age. Further investigation is warranted to study the role of certain imperative variables such as site of metastases, number of metastases, and patient co-morbidities. Survival outcomes based on primary tumor removal in metastatic low-grade GI-NETs. No 5-year survival 5-year survival Primary tumor removal without metastasectomy 1 11 No surgery 12 8

Impact of unplanned readmission to the same facility within 30 days following robot-assisted and laparoscopic hemicolectomy for early-onset non-metastatic colon cancer.

111 Background: Colon cancer in younger populations has risen in recent years, prompting changes in screening guidelines. Hemicolectomy remains integral for standard treatment for non-metastatic early-onset colon cancer, and many institutions have adopted robot-assisted approaches for this procedure. However, high costs associated with this technology along with mixed data regarding survival benefits and post-surgical complications warrant further investigations on the specific advantages of robot-assisted surgery. This study aims to examine the impact of unplanned readmission to the same facility within 30 days following surgery for patients receiving robot-assisted and laparoscopic hemicolectomy on long-term survival for early-onset non-metastatic colon cancer to see how current paradigms of colon cancer treatment extend to early-onset patients. Methods: The National Cancer Database was used to identify patients under the age of 50 receiving a minimally invasive hemicolectomy for primary non-metastatic colon cancer diagnosed between 2016-2020. Patients were stratified based on surgical approach and whether they underwent an unplanned readmission to the same facility within 30 days following surgery, and survival differences were calculated log-rank test and Cox regression analysis that included co-variates related to tumor characteristics, patient demographics, and facility characteristics. Results: 5,076 patients were identified, with 577 receiving a robot-assisted approach and 4,499 receiving a laparoscopic approach. Multivariate analysis found no significant difference in long-term survival between patients receiving a laparoscopic versus robot-assisted approach (HR: 0.893, 95% CI: 0.687-1.161, p=0.398). Additionally, multivariate analysis found that unplanned readmission within 30 days did not have a significant impact on long-term survival outcomes for patients receiving a robot-assisted approach (HR: 0.856, 95% CI: 0.257-2.848, p=0.800), but it did find worsened survival outcomes for the laparoscopic approach (HR: 1.535, 95% CI: 1.070-2.203, p=0.020). Conclusions: Patients receiving laparoscopic hemicolectomy for early-onset non-metastatic colon cancer appear to have worsened overall long-term survival outcomes when undergoing an unplanned readmission to the same facility within 30 days of surgery when compared to patients receiving a robot-assisted surgical approach. However, it also appears that overall, both surgical approaches have similar overall long-term survival. Further research on how robot-assisted surgery impacts survival and post-surgical complications in patients with early-onset non-metastatic colon cancer is warranted to examine how this advancing technology could improve cancer care.

Longitudinal impact of extended-hours hemodialysis with a liberalized diet on nutritional status and survival outcomes: findings from the LIBERTY cohort.

Protein-energy wasting (PEW), a unique weight loss linked to nutritional and metabolic abnormalities, is common in patients undergoing hemodialysis (HD) and associated with adverse outcomes. This study investigated whether extended-hours HD combined with a liberalized diet could overcome PEW and improve survival. The body mass index (BMI) and survival outcomes in patients undergoing extended-hours HD were evaluated for up to 8years using data from the LIBeralized diet Extended-houRs hemodialysis Therapy (LIBERTY) cohort. Extended-hours HD was defined as weekly dialysis length ≥ 18h. The LIBERTY cohort included 402 patients who initiated extended-hours HD. An increase in the length and frequency of HD sessions was observed over time, with approximately 70% and 20% of patients undergoing extended-hours HD for > 21h/week and > 3 sessions/week at 5years, respectively. The BMI and percentage creatinine generation rate were maintained over time, with no substantial increase in the phosphorus and potassium levels. The estimated BMI initially increased, and thereafter plateaued over time in patients with a baseline BMI < 25kg/m2, whereas it decreased gradually in patients with a baseline BMI ≥ 25kg/m2 after several years from baseline. Ninety-one patients died, and 108 discontinued extended-hours HD during the median follow-up period of 6.2years (interquartile range, 3.5-8.0), yielding a 5-year survival rate of 85%. Extended-hours HD with a liberalized diet may help achieve favorable survival outcomes and maintain nutritional status. Thus, it is a promising treatment option for managing PEW in patients undergoing HD.

Impact of comorbidity on survival in cancer patients receiving immune checkpoint inhibitors.

Immunotherapy efficacy in elderly patients with comorbidities and poor performance status is not well understood. More knowledge on this topic is needed to identify subgroups that will benefit from immunotherapy. We aimed to evaluate the effect of comorbidity burden in patients receiving immunotherapy. Patients older than 18 years of age and diagnosed with various malignancies, followed up in our tertiary cancer center were screened. Patients treated with immunotherapy were included in this study. We used to Charlson Comorbidity Index (CCI) to evaluate patients' comorbidity burden. The primary outcome was overall survival (OS). Hazard ratio (HR) with confidence interval (CI) was evaluated in multivariable analysis. A total number of 197 patients were included. The median age was 62 years. Patients were grouped based on CCI scores: CCI-low (≤ 8) and CCI-high (> 8). One-hundred and seven patients (54.9%) had metastatic disease at the time of diagnosis. Most frequently used immunotherapy agent was nivolumab (n = 124, 62.9%), followed by pembrolizumab (n = 36, 18.3%). The median OS was shorter in the CCI-high group than in the CCI-low group (10.6 vs. 21.2 months, p = 0.002) In multivariable analysis, treatment with anti-CTLA4 (HR: 1.85, 95% CI 1.07-3.20, p = 0.028), ECOG performance status (2-4 vs. 0-1) (HR: 2.17; 95% CI 1.25-3.75; p = 0.005), and higher CCI scores (CCI-high vs. CCI-low) (HR: 1.97; 95% CI 1.3-3.0; p = 0.001) were independently associated with worse OS. Comorbidity burden and performance status independently predict survival outcomes in immunotherapy-treated cancer patients. Comprehensive comorbidity assessment is essential for optimizing treatment and improving patient outcomes.

Extremely early initiation of vasopressors might not decrease short-term mortality for adults with septic shock: a systematic review and meta-analysis

BackgroundThe optimal timing for initiating vasopressor therapy in patients with septic shock remains unclear. This study aimed to assess the impact of early versus late vasopressor initiation on clinical outcomes.MethodsA systematic review and meta-analysis were conducted by searching PubMed, Embase, and Cochrane databases. Studies comparing early and late vasopressor administration in septic shock patients were included. The primary outcome was short-term mortality, and subgroup analyses were performed based on different initiation timings.ResultsEleven studies with 6,661 patients were included. Different studies define the ‘early administration’ timeframe variously, ranging from one to seven hours. No significant difference in short-term mortality was observed between early and late administration in the combined analysis of 3,757 patients from two RCTs and three quasi-experimental studies (OR: 0.66, 95% CI: [0.36, 1.19], I²: 82%). However, lower mortality was found in subgroups with early but not extremely early initiation (one to three hours, OR: 0.70, 95% CI: [0.60, 0.82], I²: 0%), and those using septic shock diagnosis as time zero (OR: 0.64, 95% CI: [0.48, 0.85], I²: 39%).ConclusionOur findings found that earlier initiation of vasopressor therapy, particularly within one to three hours after the diagnosis of septic shock, may be associated with reduced short-term mortality in certain subgroups. However, due to the heterogeneity in study definitions and potential confounding factors, these results should be interpreted cautiously. Further standardized investigations are warranted to precisely determine the optimal timing for vasopressor initiation to maximize survival outcomes in patients with septic shock.