Appendiceal Cancer Research Articles

Ascites as a Predictive Factor in Malignancies in the Last Year of Life-Comparison Between Different Cancer Types.

Background: Ascites in malignancies is usually associated with poor prognosis, but the predictive value may vary between different cancer types. Objectives: The aim was to map the frequency and temporal pattern of paracentesis in patients with malignancies in relation to time to death and to evaluate the occurrence of ascites as a predictive factor in different cancer types, with a limitation to the last year of life. Design: A retrospective study based on registry data covering all care visits in the Stockholm Region, Sweden, for seven years was performed. All deceased subjects that had at least one registered paracentesis in the last year of life were included. Results: Of 23,056 subjects dying from cancer, 1863 had undergone paracentesis in the last year of life (8.0%). Ascites requiring paracentesis was most frequently seen in appendiceal cancer (38%), ovarian cancer (35%), cholangiocarcinoma (26%), hepatocellular carcinoma (19%), and pancreatic cancer (17%). The median time for the first paracentesis in all cancer types varied between 248 and 20 days before death. For ovarian cancer, the median time for first paracentesis differed significantly compared with upper gastro-intestinal (GI) cancers, 81 days compared with 30 days (p < 0.0001). Ascites in prostate cancer was rare,1.9%, but when present, a pronounced increase in the frequency of paracentesis was observed in the last three months of life. Conclusion: The occurrence of paracentesis in patients with advanced cancer is generally a sign that death is approaching within the coming months, especially in upper GI cancer. For ovarian and appendiceal cancers, ascites is less useful as a predictive tool.

ASO Visual Abstract: Decision Regret in Appendiceal Cancer Patients Undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

ASO Visual Abstract: Decision Regret in Appendiceal Cancer Patients Undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

Systemic inflammatory markers: Predictors of survival in mucinous appendix cancer patients treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy

IntroductionInflammatory markers have been investigated as predictors of prognosis in various malignancies, but their role in mucinous appendix cancer (MAC) remains controversial. We evaluated the association between complete blood count-derived markers and survival in MAC patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). MethodsWe conducted a retrospective analysis of a single-center database (1998–2023) including newly diagnosed MAC patients who underwent complete (CC-0/1) CRS/HIPEC. Preoperative values of neutrophil-to-lymphocyte ratio (NLR), derived NLR, platelets-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) were calculated. For markers strongly associated with survival, we used time-dependent ROC analysis to define cutoffs to predict 5-year overall survival (OS). The Kaplan-Meier method with and Cox regression were employed for survival analysis. ResultsOf 626 CRS/HIPEC cases, 211 were eligible. NLR (p=0.049), dNLR (p=0.049), and MLR (p<0.001) were significantly associated with OS, while PLR was not. MLR demonstrated the strongest prognostic power (AUC=0.682) with the optimal cut-off 0.29. There were no significant differences in age, grade, or peritoneal cancer index (PCI) between patients with MLR<0.29 and MLR≥0.29. Five-year progression-free (PFS) and OS were 72.2 % and 83.2 % for MLR<0.29 and 54.2 % and 66.6 % for MLR≥0.29, respectively. After adjusting for age, PCI, and grade, MLR≥0.29 was associated with worse 3-year PFS (hazard ratio [HR] 1.74, 95 % confidence interval [CI]:1.02–2.97, p=0.044) and 3-year and 5-year OS (HR 1.87, 95 %CI: 1.00–3.47, p=0.049). ConclusionMLR has emerged as an independent predictor of survival in MAC patients undergoing CRS/HIPEC. Along with other prognostic factors, MLR≥0.29 may be potentially used for preoperative risk stratification.

Prognostic factors of early recurrence after complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

Although cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) offer the potential for long-term survival in peritoneal carcinomatosis, outcomes following CRS/HIPEC vary significantly. To identify the clinical factors associated with progression-free survival (PFS) after complete CRS/HIPEC in patients with colorectal/high-grade appendiceal, ovarian, and gastric cancers. We retrospectively evaluated the risk of recurrence within 1 year after CRS/HIPEC and its impact on overall survival (OS) in patients recruited between 2015 and 2020. Logistic regression models were used to assess the prognostic factors for the risk of recurrence within 1 year. Kaplan-Meier survival curves and Cox proportional hazards models were used to evaluate the association between recurrence and OS. Of the 80 enrolled patients, 39 had an unfavorable PFS (< 1 year) and 41 had a favorable PFS (≥ 1 year). Simple logistic models revealed that the patients with a completeness of cytoreduction score of 0 (CC-0) or length of CRS ≤ 6 h had a favorable PFS [odds ratio (OR) = 0.141, P = 0.004; and OR = 0.361, P = 0.027, respectively]. In multiple logistic regression, achieving CC-0 was the strongest prognostic factor for a favorable PFS (OR = 0.131, P = 0.005). A peritoneal cancer index score > 12 was associated with a lower rate of achieving CC-0 (P = 0.027). The favorable PFS group had a significantly longer OS (median 81.7 mo vs 17.0 mo, P < 0.001). Achieving CC-0 was associated with a lower early recurrence rate and improved long-term survival. This study underscores the importance of selecting appropriate candidates for CRS/HIPEC to manage peritoneal carcinomatosis.

Successful management of renal abscess secondary to diabetes mellitus with surgical treatment and hyperbaric oxygen therapy

ABSTRACT Yanagida K, Watanabe D, Yoshida T, Nakagawa T, Mizushima A, Miura K, Ishihara T. Successful management of renal abscess secondary to diabetes mellitus with surgical treatment and hyperbaric oxygen therapy. Undersea Hyperb Med. 2024 Third Quarter; 51(3):231-235. Renal abscess (RA) is a collection of infective fluid in or around the renal parenchyma. It typically occurs in immunocompromised patients, including those with diabetes mellitus (DM), poor nutritional status, or steroid administration. We herein report a case of RA associated with DM in which hyperbaric oxygen (HBO2) therapy greatly contributed to the resolution of this disease. The patient was an 85-year-old man with poorly controlled type 2 DM. Contrast-enhanced computed tomography for postoperative follow-up of appendiceal cancer showed a mass lesion with poor contrast enhancement extending from the upper pole of the left kidney to the dorsal side. Therefore, a diagnosis of RA was established. The lesion was percutaneously punctured, and a drainage tube was placed. Antibiotics following sensitivity testing were administered. The catheter was removed six days after its placement. However, pus discharge continued from the catheter removal site, with persistent redness around the wound. Therefore, a lumbotomy incision for abscess drainage was performed on the 49th day. However, the pus discharge persisted, and we decided to perform HBO2 therapy, expecting decreases in bacterial proliferation, reduction in local edema, and improvement of host defense. HBO2 therapy for 90 min at two atmospheres absolute was performed ten times. The amount of pus discharge decreased, and redness improved from the fifth day after HBO2 therapy. One month after starting HBO2 therapy, the wound was closed, and the pus discharge resolved completely. Four years have passed since the HBO2 therapy, and there have been no symptomatic or imaging relapses of RA. Keywords: hyperbaric oxygen therapy; renal abscess; SGLT2 inhibitor; type 2 diabetes mellitus

EP452 - Outcomes of Appendiceal Cancer Over 10 Years in a District General Hospital

Abstract Aims To evaluate outcomes of appendiceal tumour patients at a district general hospital. Methods A retrospective review was performed to detect patients (16 years or older) with positive histology findings of appendiceal cancers post appendicectomy or colectomy between January 2014 to January 2024. Data was collected from a prospectively maintained electronic patient hospital record (Meditech, Version 6, USA). Results 13 patients were diagnosed to have appendiceal tumours between January 2014 – January 2024. Median age of presentation was 53 (IQR 43).Total Patient Number13Male30.8%Female69.2%Appendiceal Tumour TypePercentage of Appendiceal Tumour PatientsCarcinoid (Neuroendocrine)76.9%Adenocarcinoma7.7%Low Grade Mucinous15.4%High Grade Mucinous0% Median length of stay was 2.5 days (IQR 2.25). Emergency presentations made up 76.9% of admissions. Appendicectomy was the primary operation for 92.3%. 75% of tumours were &amp;lt;1cm, with 25% of tumours &amp;gt;1cm. Location of tumour was predominantly involving the tip in 61.5% of cases, with body and base involvement being 23.1% and 15.4% respectively. Tertiary referral was made for 84.6% of patients. 15.4% had evidence of metastatic disease. Subsequently 15.4% of patients had hyperthermic intraperitoneal chemotherapy (HIPEC), with 7.7% having HIPEC and systemic chemotherapy and radiotherapy. Conclusions Carcinoid (neuroendocrine) was the most common type of appendiceal tumour, mostly presenting as an emergency appendicitis. It was more commonly diagnosed in females. While appendiceal cancers are very rare, outcomes remained good with 100% five-year survival, demonstrating the importance of prompt tertiary referral if further treatment is required.

Mutational Features and Tumor Microenvironment Alterations in High-Grade Appendiceal Cancers Treated With Iterative Hyperthermic Intraperitoneal Chemotherapy.

High-grade appendiceal adenocarcinomas (HGAA) with peritoneal metastases (PMs) are associated with poor survival. Hyperthermic intraperitoneal chemotherapy (HIPEC) is a novel treatment approach for unresectable HGAA-PM. However, its influence on immunogenomic profiles has not yet been fully explored. We obtained 79 samples of metastatic peritoneal tumor deposits from patients diagnosed with HGAA and performed whole-exome sequencing, RNA sequencing, and immunoprofiling before and after HIPEC. Tumor biopsies were subjected to immunogenomic profiling to detect mutational signatures and immune populations associated with oncologic outcomes. Fifteen patients with HGAA-PMs were included in the study. The median progression-free survival (PFS) was 6.7 months (2.7-25.3) and the median overall survival was 11.4 months (4.7-42). Mucin-associated genes (MUC16, MUC3A, and MUC5AC) and titin (TTN) had the highest mutation frequencies. Mutational signatures such as single-base substitution 29 and doublet-base substitution 11 were present in >50% of single-base and double-base mutations. Higher PD-L1 coexpression on CD8+ T cells demonstrated a higher PFS both intratumorally (P = .019) and at the margin (P = .025). HIPEC-associated mutational signatures were identified in HGAA-PMs. Elevated PD-L1+ cytotoxic T-cell populations after HIPEC had better PFS, offering valuable insights for prognostication in the context of HIPEC treatment.

11P Therapeutic effects of MRTX1133 in KRAS G12D mutant appendiceal cancer: Insights from organoid and in vivo studies

11P Therapeutic effects of MRTX1133 in KRAS G12D mutant appendiceal cancer: Insights from organoid and in vivo studies

Self-Adaptive Teacher-Student framework for colon polyp segmentation from unannotated private data with public annotated datasets.

Colon polyps have become a focal point of research due to their heightened potential to develop into appendiceal cancer, which has the highest mortality rate globally. Although numerous colon polyp segmentation methods have been developed using public polyp datasets, they tend to underperform on private datasets due to inconsistencies in data distribution and the difficulty of fine-tuning without annotations. In this paper, we propose a Self-Adaptive Teacher-Student (SATS) framework to segment colon polyps from unannotated private data by utilizing multiple publicly annotated datasets. The SATS trains multiple teacher networks on public datasets and then generates pseudo-labels on private data to assist in training a student network. To enhance the reliability of the pseudo-labels from the teacher networks, the SATS includes a newly proposed Uncertainty and Distance Fusion (UDFusion) strategy. UDFusion dynamically adjusts the pseudo-label weights based on a novel reconstruction similarity measure, innovatively bridging the gap between private and public data distributions. To ensure accurate identification and segmentation of colon polyps, the SATS also incorporates a Granular Attention Network (GANet) architecture for both teacher and student networks. GANet first identifies polyps roughly from a global perspective by encoding long-range anatomical dependencies and then refines this identification to remove false-positive areas through multi-scale background-foreground attention. The SATS framework was validated using three public datasets and one private dataset, achieving 76.30% on IoU, 86.00% on Recall, and 7.01 pixels on HD. These results outperform the existing five methods, indicating the effectiveness of this approach for colon polyp segmentation.

Decision Regret in Patients with Appendiceal Cancer Undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

Decision regret is an emerging patient reported outcome. The aim of this study was to assess the incidence of regret in patients with appendiceal cancer (AC) who underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). An anonymous survey was distributed to patients through the Appendix Cancer and Pseudomyxoma Peritonei (ACPMP) Research Foundation. The Decision Regret Scale (DRS) was employed, with DRS > 25 signifying regret. Patient demographics, tumor characteristics, postoperative outcomes, symptoms (FACT-C), and PROMIS-29 quality of life (QoL) scores were compared between patients who regretted or did not regret (NO-REG) the procedure. A total of 122 patients were analyzed. The vast majority had no regret about undergoing CRS-HIPEC (85.2%); 18 patients expressed regret (14.8%). Patients with higher regret had: income ≤ $74,062 (72.2% vs 44.2% NO-REG; p = 0.028), major complications within 30 days of surgery (55.6% vs 15.4% NO-REG; p < 0.001), > 30 days hospital stay (38.9% vs 4.8% NO-REG; p < 0.001), a new ostomy (27.8% vs 7.7% NO-REG; p = 0.03), >1 CRS-HIPEC procedure (56.3% vs 12.6% NO-REG; p < 0.001). Patients with worse FACT-C scores had more regret (p < 0.001). PROMIS-29 QOL scores were universally worse in patients with regret. Multivariable analysis demonstrated > 30 days in the hospital, new ostomy and worse gastrointestinal symptom scores were significantly associated with regret. The majority of patients with AC undergoing CRS-HIPEC do not regret undergoing the procedure. Lower income, postoperative complications, an ostomy, undergoing > 1 procedure, and with worse long-term gastrointestinal symptoms were associated with increased regret. Targeted perioperative psychological support and symptom management may assist to ameliorate regret.

Minimum number of lymph nodes to maximize survival in non-metastatic appendiceal adenocarcinoma

IntroductionIn non-metastatic appendiceal adenocarcinoma, the relationship between the number of lymph nodes harvested and overall survival is unknown. The objective of this study was to determine whether the number of lymph nodes harvested impacts survival in patients with mucinous and non-mucinous appendiceal cancer. MethodsRetrospective cohort analysis was conducted in patients who underwent surgery for appendiceal adenocarcinoma in the SEER database from 2000–2019. Exclusion criteria included patients without the number of regional nodes harvested/node positivity, missing survival data, stage IV disease, and certain subtypes of appendiceal tumors. The primary outcome was 10-year overall survival. ResultsA total of 1651 patients were identified, 1101 with mucinous and 550 with non-mucinous cancer. The majority of patients were male (54 %) and between the ages of 50–74 (52 %). Mean ± SD number of lymph nodes harvested was 17.04 ± 10.41. The ten-year survival rates for patients with mucinous appendiceal cancer were 43–74 % and 25–68 % for non-mucinous cancer, depending on AJCC stage. Multivariate Cox-regression analysis displayed that the number of lymph nodes harvested was an independent predictor of survival (p < 0.0001). The optimal threshold predicted by Cox-regression for maximal survival benefit was harvest of a minimum of 15 nodes for mucinous and 12 for non-mucinous cancer. Additionally, for mucinous cancer, per each additional 3 nodes harvested past 15, the 10-year risk of mortality decreased by 7 % (HR 0.93 (0.88 to 0.98), p < 0.001). ConclusionsThe number of lymph nodes harvested is an independent predictor of survival for patients with appendiceal adenocarcinoma. To maximize this survival benefit, a minimum of 15 regional lymph nodes must be harvested for mucinous and 12 for non-mucinous cancer.

Risk factors of a positive resection margin in locoregional appendix cancer and its impact on survival: The national cancer database analysis

IntroductionThe impact of a positive resection margin (RM+) in appendiceal cancer (AC) remains unclear, with small studies suggesting it does not worsen survival in low-grade subtypes. We aimed to evaluate RM+ rates, its risk factors, and survival outcomes across different AC histologies. MethodsWe conducted a multicenter retrospective cohort study using the National Cancer Database (2004–2019) and including stage I-III AC cases. Surgical and survival outcomes were compared between RM+ and RM- groups, with logistic regression analyzing the association of RM+ and its predictors. Subgroup analysis was performed for low/high tumor grade (LG/HG), mucinous/non-mucinous pathology (MAC/NMAC), and signet ring cell carcinoma (SRC). ResultsAmong 6800 patients identified, 737 (10.8 %) had RM+, while 6063 (89.2 %) had RM-. RM+ rates varied across AC histologies: 10.9 % in LG-MAC, 17.0 % in HG-MAC, 7.8 % in LG-NMAC, 13.9 % in HG-NMAC, and 17.9 % in SRC. RM+ correlated with significantly worse survival in LG-MAC (HR 1.67), HG-MAC (HR 1.83), LG-NMAC (HR 2.04), and SRC (HR 2.37) but not in HG-NMAC after adjusting to other factors. Predictors of RM+ included pT stage, preoperative chemotherapy in LG tumors and pT stage and positive lymph nodes in HG tumors whereas more extensive resection was associated with RM- in both LG and HG. ConclusionRM+ worsens survival in most AC subtypes, highlighting the importance of achieving negative margins. Extensive resection, like right hemicolectomy, can improve RM- rate, but factors such as pT stage, lymph node status, and preoperative chemotherapy also affect RM+. Surgeons should prioritize achieving RM- in all AC histologies.

Travel distance does not affect overall survival in patients with appendiceal adenocarcinoma undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy

IntroductionCytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is a potentially curative approach for appendiceal cancer (AC) with peritoneal dissemination and is most often employed at tertiary referral centers. Regionalization may provide geographic barriers to care for vulnerable patients. The aim of this study was to examine the effect of travel distance on oncologic outcomes of patients with AC treated with CRS-HIPEC. MethodsThe National Cancer Database (NCDB) was reviewed from 2006 through 2020 for patients with AC who underwent CRS-HIPEC. The primary comparison variable was distance (<50 miles vs ≥ 50 miles from the CRS-HIPEC facility). Demographic and tumor characteristics were analyzed. Primary outcome was overall survival (OS). Secondary outcomes were 30-day and 90-day mortality, readmission, and length of stay (LOS). ResultsDuring the study period, 1703 patients met inclusion criteria, with 1000 patients travelling < 50 miles for CRS-HIPEC (59 %) and 703 travelling ≥ 50 miles (41 %). Patients who traveled ≥ 50 miles were more likely to be non-Hispanic White (p < 0.001), have annual income less than $74,062, be treated at an academic center and live in the South-Atlantic region of the United States. There was no significant difference in OS between groups (Figure 1). There were no significant differences in 30-day postoperative survival, 90-day survival, or 30-day readmission. Post-operative LOS was 8.0 versus 9.0 days (p < 0.001). ConclusionsTravel distance ≥ 50 miles was not significantly associated with decreased OS or increased postoperative mortality, suggesting that regionalization of care does not worsen oncologic outcomes for patients with AC undergoing CRS-HIPEC.

KRAS mutations and their prognostic implications in appendiceal cancers.

4177 Background: Despite shared embryonic origin, appendiceal cancers (AC) have distinct clinical and molecular features compared to colorectal cancers (CRC). Detection of mutant KRAS has been associated with worse survival in CRC, whereas in AC the prognostic significance of mutant KRAS (55-65% prevalence) has yet to be characterized. Methods: AC tissues from 852 individual patients that underwent DNA (592, NextSeq, or whole exome sequencing) and whole transcriptome sequencing (NovaSeq) at Caris Life Sciences (Phoenix, AZ) were analyzed. Low-grade appendiceal mucinous neoplasms were excluded. Chi-square, Fishers-exact, and Mann Whitney U tests were used to determine statistical significance and were adjusted for multiple hypothesis testing (p&lt; 0.05). Real-world overall survival (OS) was calculated using insurance claims of AC patients from time of sample collection to last contact. Hazard ratios (HRs) were calculated using the Cox proportional hazards model (log-rank test). Multivariate regression analysis was performed on age, sex, histology, site, comutations and KRASmut vs. KRASwt. Results: AC histological subtypes comprised mucinous adenocarcinoma (37.9%), goblet cell carcinoma (19.6%), signet ring cell carcinoma (12.1%), and adenocarcinoma- not otherwise specified (NOS, 30.4%). Among all AC specimens, KRAS was the most common mutation (49%). KRASmut vs. KRASwt tumors were more frequently associated with TP53mut (51.2% vs. 36.8%, respectively; p&lt; 0.01) and GNASmut (41.1% vs. 5.7%, respectively; p &lt; 0.00001). Most frequent co-mutant gene with KRAS was TP53 (61.2%) in adenocarcinoma-NOS, and GNAS (46.9%) in mucinous adenocarcinomas.Median OS among KRASmut vs. KRASwt was 33.3 vs. 25.1 months, respectively (HR 0.68, 95% CI: 0.58-0.80, p &lt; 0.00001). KRASmut was associated with improved survival in mucinous adenocarcinomas (HR 0.71; 95% CI: 0.52-0.96, p = 0.028) and adenocarcinoma-NOS (HR 0.77; 95% CI: 0.62-0.97, p = 0.025), but not with signet ring cell (HR 1.92; 95% CI: 0.90-4.10, p = 0.087) or goblet cell carcinoma (HR 1.39; 95% CI: 0.50-3.91, p = 0.536). Multivariate analysis showed KRASmut was an independent prognostic factor for improved survival among all AC (HR 0.77, 95% CI: 0.64-0.93, p = 0.007) and mucinous adenocarcinoma (HR 0.60, 95% CI: 0.42-0.84, p&lt;0.0001).Notably, GNASmut was associated with improved survival (HR 0.57, 95% CI: 0.47-0.70, p &lt; 0.00001), while TP53mut was associated with poorer survival (HR 1.58, 95% CI: 1.35-1.86, p &lt; 0.00001) among all AC. Conclusions: KRAS was one of most frequently mutated genes in ACs. In contrast to CRC, KRASmut was associated with significantly improved survival. This observed survival advantage remained consistent in the histologic subgroup of mucinous adenocarcinoma, but not in goblet and signet ring cell cancers. Further studies with population level data understanding the molecular profiles and their survival implications in histologically distinct AC are needed.

Enhancing appendiceal cancer care: Towards evidence-based practice and continuous education for healthcare providers.

e16377 Background: Appendiceal cancers (AC) are a set of rare and histologically diverse malignancies with distinct biological features and treatment implications. Despite surgical advances, there are gaps in the standardization of systemic therapies for AC. Hence, there is a pressing need to understand the current practice patterns amongst oncologists to facilitate unifying management strategies. Methods: A cross-sectional survey was distributed electronically among GI oncology specialists between April – October 2023 to map current practices in AC care. The survey contained 18 questions structured in three sections— participant demographics, treatment experiences, and management preferences for hypothetical cases. The analysis focused on response frequencies informing the need to develop targeted educational and research initiatives. Results: Most of the respondents (N = 104; response rate 22%), primarily from academic (86%) and urban settings (77%), manage up to 10 AC patients annually. Despite over five years of practice experience for 80% of respondents, high confidence in treating AC was modest (38%). The majority (83%) cited lack of guidelines and standardized treatments as a concern. The NCCN guidelines were commonly referred to, but only 13% were satisfied with AC education. For intermediate and high-grade AC, 63% and 53%, respectively, of respondents reported using perioperative chemotherapy with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. 40% opted for systemic therapy for low-grade neoplasms. 5FU/Capecitabine and oxaliplatin were the most common regimens of choice, whereas irinotecan, anti-VEGF, and anti-EGFR agents were used less frequently. Surveillance primarily involved serum CEA (91%) and CT scans (99%), with PET, MRI, and ctDNA used by 20-30% of the respondents. Free-text comments noted deficient evidence and educational needs to guide clinical practice. Conclusions: Our study is the first to describe physician attitudes and practice patterns in the management of AC. The survey highlights that even experienced providers feel underconfident when treating AC patients and supports the need for better evidence and data for systemic therapies. About 40% of the respondents noted offering chemotherapy to low grade neoplasms – a disease that is not thought to respond to systemic therapy, highlighting the need for education and clinical trials to guide evidence-based decision-making in this disease. In addition, multidisciplinary, multi-institutional efforts to unify treatment approaches and enhance patient outcomes are needed.

Association of circulating DNA with recurrence in CRS-HIPEC patients with colorectal and appendiceal peritoneal carcinomatosis: Insights from a phase II randomized trial.

3598 Background: There is a need for biomarkers to guide patient selection for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) in cases of peritoneal carcinomatosis from colorectal and appendiceal cancer. SigNatera is a blood-based quantitative test to detect colorectal cancer recurrence by indicating the presence of at least two altered colorectal cancer-associated genes in Circulating tumor DNA (ctDNA). We performed a correlative study to help determine if using SigNatera ctDNA would be a predictive and prognostic biomarker of recurrent cancer in patients who underwent CRS-HIPEC on a Phase II Randomized Trial Comparing Morbidity and Mortality of CRS-HIPEC using Mitomycin-C versus Melphalan for Colorectal and Appendiceal Peritoneal Carcinomatosis. Methods: 30 patients on the phase II trial had the option for consenting for the ctDNA correlative study utilizing SigNatera sponsored by Natera. Pre-op samples were collected prior to CRS-HIPEC on Day 0 and post-op samples ~2 weeks post-hospital discharge, followed by every 3 months x 2 years. The exploratory objective of the prognostic impact of ctDNA is evaluated by correlating pre-op ctDNA status and Disease-Free Survival (DFS) Results: All 30 pts that underwent ctDNA testing were treated with neoadjuvant chemotherapy prior to CRS-HIPEC. Pre-op ctDNA was negative in 20 pts (8 recurrences, median DFS = 15.9 months) and positive in 10 pts (7 recurrences, median DFS = 39.9 months), p =0.19. Of the 20 pre-op ctDNA(-) pts, 18 remained ctDNA(-) in post-op (12 recurrences, median DFS = 15.6 months) and 2 turned ctDNA(+) (0 recurrences). Of the 10 pre-op ctDNA(+) pts, 2 remained ctDNA(+) post-op (1 recurrence, median DFS = 9.5 months) and 8 turned ctDNA(-) (2 recurrences, median DFS = 39.9 months), p=0.1. Conclusions: The unexpected numerically favorable DFS in the pre-op ctDNA(+) group, in comparison to the pre-op ctDNA(-) group, challenges the utility of preop ctDNA status in guiding CRS + HIPEC decision-making. Though limited by small sample size, this finding may be likely due to the impact of post-op therapy which notably converted 10 preop ctDNA(+) pts to post-op ctDNA(-) status. Our findings warrant validation in a larger study to unravel the multifaceted factors influencing ctDNA’s prognostic value. Clinical trial information: NCT03073694 . [Table: see text]

A phase I/II study of intraperitoneal (IP) paclitaxel (PTX) in patients with metastatic appendiceal adenocarcinoma.

TPS4215 Background: Appendiceal cancer is a rare, orphan disease, that is unfortunately becoming more common. There is growing data from our lab and others that particular subtypes of AA do not respond to CRC chemotherapy. The use of CRC chemotherapy to treat patients with AA tragically results in many patients enduring side effects from chemotherapy that is ineffective; however, this practice will likely continue unless AA-specific treatments are developed. The Shen lab has recently tested IP paclitaxel (PTX) in orthotopic PDX models of AA. After allowing implanted tumors to grow for four weeks to simulate diffuse peritoneal metastases, baseline MRI was performed and mice were randomly assigned to treatment groups of four mice and intraperitoneally (IP) administered increasing doses of PTX. Marked response was seen in all three models at dose of 25 mg/kg IP weekly, with a near complete response in model AAPDX-10. This dose given IP was well tolerated by the mice, notably this dose exceeds the know lethal IV PTX dose. Methods: The Phase I component of this study will be a prospective single-arm intervention trial giving IP PTX every 2 weeks for a total of 5 doses with primary endpoint of safety and tolerability (MTD determination). Each patient will have an initial diagnostic laparoscopy where PCI score will be calculated and IP catheter placed, dx lap is repeated at the end of study after 5 biweekly doses. For the Phase 1 portion of the trial a Bayesian Optimal Interval (BOIN) approach will be used to determine recommended phase 2 dose (RP2D). All patients treated at that dose or higher will be included in Phase 2 component of the study where the primary objective is response, determined by change in PCI score. With 15 patients Based on historical data, we estimate that the proportion of patients who will demonstrate an objective response without going on trial is 0.05, i.e., the null hypothesis is a 0.05 ORR. Treatment is expected to raise this proportion to 30%. Using an exact binomial test with one-sided type I error of 0.05, we will reject the null if at least 3 patients achieve response. This test has power of 87%. Secondary end points include pathologic, biochemical and radiographic response, PFS, OS, and the influence of KRAS/GNAS/TP53 mutation on response. PK measurements will also be performed during the Phase 1 portion of the trial to determine the degree to which the IP injected PTX enters the blood stream. Patients will be followed for up to 1 year. Adverse events (AEs) will be captured and graded using the National Cancer Institute’s (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) v. 5.0 (or latest version) and will include the event term, grading, duration and attribution. Attribution to the study agent or intervention will be determined by the PI, Co-PI or treating physician. Clinical trial information: NCT06207305 . [Table: see text]

Early-onset appendiceal adenocarcinoma (EOAA): 10-year experience from a single center.

4178 Background: The incidence of early-onset (age &lt;50) gastrointestinal cancers, including early onset Appendiceal Adenocarcinoma (EOAA) is on the rise, however reported data on etiology, treatment, and outcomes is scarce. Here we present outcomes for EOAA patients treated at a single high-volume center. Methods: Records of patients (pts) with EOAA were reviewed. Clinicopathological and genomic data were abstracted. Pts aged 18 - 49 years at diagnosis with Appendiceal Adenocarcinoma (AA) seen at UCMC between 2013 - 2023 were included. The primary outcome of Overall survival (OS) was analyzed using univariable Cox proportional hazards regression analysis. Results: 116/492 (23.6%) appendix cancer pts seen at UCMC had early-onset disease. 45 pts met eligibility (Table). 10/20 (50%) pts with localized disease had recurrence after hemicolectomy (median recurrence free survival = 41.6 months; 95% CI, 34.3 – NR; follow-up = 46.42 months). 22/44 (50%) pts had mucinous AA, 21 (47.7%) goblet cell AA, and 1 (2.33%) had poorly differentiated AA. In 35 pts with metastatic/recurrent disease, mOS was 35.93 months (95% CI, 28.4 – NR). Lymphovascular (LVI) or perineural invasion (PNI) (HR, 6.41; 95% CI, 2.10 – 19.59, p = 0.001), lymph nodes metastasis (HR, 13.11; 95% CI, 3.53 – 48.68; p &lt; 0.001), and grade 3 disease (vs. grade 1; HR, 5.28; 95% CI, 1.43 – 19.51, p = 0.01) were prognostic for worse OS in univariable analysis. Cytoreductive surgery (CRS), irrespective of completeness, was associated with improved OS (HR = 0.21; 95% CI, 0.09 – 0.53; p &lt; 0.001). Next Generation Sequencing results were available in 20 cases: KRAS (n = 10, 50%), TP53(n = 7, 35%), GNAS (n = 6, 30%), SMAD4 (n = 4, 20%), and MYC (n = 3, 15%) were frequently altered. Alterations with potential therapeutic targets were seen in 12/20 (60%) cases. 10 pts had germline testing with 2 (20%) pathogenic alterations detected: SDHA(H447Mfs*23) and CHEK2 (T367Mfs*15). The pt with CHEK2 mutation had AA as the only malignancy, was the youngest (age 26.17) and passed away 17.26 months after diagnosis. Conclusions: A considerable number of patients with AA may have early-onset disease. A median OS of about 3 years in this young and vulnerable patient population is alarming. As in late-onset disease, EOAA is often incidentally diagnosed. LVI or PNI may be associated with poorer outcomes and deserve additional consideration for risk stratification. Many patients have targetable genomic alterations and should be included in clinical trials where current enrollment is often unsatisfactory for AA. Germline mutation testing in patients with EOAA should be widely implemented. [Table: see text]

Outcomes of patients with peritoneal carcinomatosis treated with HIPEC and chemotherapy or HIPEC alone: A single center community experience.

e15578 Background: Peritoneal carcinomatosis is a common presentation of intraperitoneal malignancies. The optimal management of peritoneal carcinomatosis is currently unknown but can contain a combination of HIPEC and chemotherapy. Optimal timing and order of these interventions is controversial. HIPEC surgery alone can provide a cure rate of approximately 16% with macroscopically complete resection. The PRODIGE 7 trial demonstrated no difference in overall survival between HIPEC plus cytoreduction versus cytoreduction alone with six months of systemic chemotherapy. Which patients should receive HIPEC, chemotherapy and HIPEC or chemotherapy alone remains unknown. Methods: This is a single center, retrospective chart review assessing all patients age 18 and above who received HIPEC surgery with and without the administration of chemotherapy at Ascension Saint John Hospital. Results: We found that there was no significant difference in overall survival and progression free survival between the HIPEC and HIPEC with chemotherapy group with a OS of 57.2 months and 52.5 months; and PFS of 33.6 and 34.4 months respectively. We found that patients with a PCI score between 0 and 13, overall survival favored the HIPEC alone group versus the HIPEC with chemotherapy with a p value of 0.043. There was no difference in progression free survival and overall survival in all other groups when stratified by PCI. When stratified by disease subtype, we no differences between PFS and OS for both appendiceal and colon cancer. Conclusions: The primary objective of this study was to investigate the difference in overall survival and progression free survival among patients with peritoneal carcinomatosis when treated with either HIPEC with systemic chemotherapy versus HIPEC alone. This analysis among 100 patients showed no statistically significant differences in OS or PFS for patients receiving a combination of HIPEC with systemic chemotherapy versus HIPEC alone. The only exception to this was with respect to OS in patients with a PCI score between 0-13. In this group, 0 patients in the HIPEC along group experienced disease progression where 5 progressed in the HIPEC and chemotherapy group. Our data suggests that HIPEC alone may be a reasonable treatment approach for patients with a low PCI score. Important conclusions can be drawn from the data when compared to historical trials. The PROTEGE 7 study found that the median overall survival was approximately 41.7 months for the HIPEC and cytoreductive surgery group and 41.2 months versus cytoreductive surgery alone. The overall survival for the HIPEC alone group was 57.2 months and 52.5 months for the HIPEC plus chemotherapy group. This data suggests that the combination of HIPEC and chemotherapy is a reasonable approach to patients with peritoneal carcinomatosis.

ASO Author Reflections: Innovative HIPEC Organoid Models and Mucolytics: Targeted Therapeutic Use of Bromelain for Appendiceal Cancer.

ASO Author Reflections: Innovative HIPEC Organoid Models and Mucolytics: Targeted Therapeutic Use of Bromelain for Appendiceal Cancer.