Small Bowel Tumors Research Articles

P25-5 Effective treatment of chemotherapy with EGFR Ab for an unresectable Lynch syndrome-associated small intestinal cancer

Lynch syndrome is a hereditary disease caused by germline variants of the MMR gene, which impairs the MMR mechanism and results in MSI, leading to canceration. In recent years, it has been reported that ICI is effective for cancers in which the MMR mechanism is impaired, but there are few reports showing the effectiveness of cytotoxic and molecular-targeted agents.

Survival of patients with small bowel neuroendocrine neoplasms in Auckland, Aotearoa New Zealand.

BackgroundSmall intestinal Neuroendocrine Neoplasms (SI‐NENs) are the most common primary malignancy of the small bowel. The aim of this study is to define the survival of patients with an SI‐NEN in Auckland, Aotearoa New Zealand (AoNZ).MethodsA retrospective study of all patients diagnosed with a jejunal or ileal SI‐NEN in the Auckland region between 2000 and 2012 was performed. The New Zealand NETwork! Registry was searched to identify the study cohort. Retrospective data collection was performed to collect stage, survival and follow up data.ResultsOne hundred and seven patients were included in the study. The mean age of patients was 62.8 years (SD 11.9). The 5 and 10‐year disease‐specific survival for all patients was 66.1% (95% CI 56.5–75.7%) and 61.8% (95% CI 51.8–71.8%), respectively. Ten‐year disease‐specific survival was 100% for stage I and II, 74% (95%CI 61.7–84.4%) for stage III and 33.9% (95%CI 16.9–35.6%) for stage IV SI‐NEN. Eleven of 40 (27.5%) patients with stage III disease had recurrence and 3 of 7 (42.8%) patients with stage IV disease had recurrence. In patients with stage IV disease, neither primary resection (HR 2.25, 95% CI 0.92–5.5) nor distant resection (HR 1.72, 95% CI 0.63–4.7) were significantly associated with a disease‐specific or overall survival benefit.ConclusionThis study demonstrates that stage at SI‐NEN diagnosis is associated with survival, but resection of the primary or distant metastases in patients with stage IV disease is not. There was no recurrence in patients with stage I or II disease after complete resection.

The analysis of prognostic factors of primary small intestinal gastrointestinal stromal tumors with R0 resection: A single-center retrospective study.

Objective:We aim to assess factors that affect overall survival in patients with primary small intestinal gastrointestinal stromal tumors (GISTs) who had undergone R0 resection.Method:A retrospective analysis reviewed the data of 82 consecutive confirmed GIST patients at a single medical center in China from January 2012 to June 2020. The survival curve was estimated using the Kaplan–Meier method, and independent prognostic factors were confirmed using the Cox regression model.Results:A total of 82 patients were included in the study: 42 men and 40 women, the mean age was 59 years old (23–83 years old). Tumors were commonly found in the jejunum (46.3%), ileum (20.7%), and duodenum (32.9%). The median tumor size was 6.0 cm (range: 1.0–15.0 cm). The number of mitoses per one 50 high-power field was used to define the mitotic rates. In our present study, 56 patients presented a mitotic rate ≤5 (68.3%) and 26 patients showed a rate >5 (31.7%) at the time of diagnosis. All patients accepted tumor resection without lymph node resection. The positivity rate was 97.6% for CD117, 96.3% for delay of germination 1, 65.9% for CD34, 6.1% for S-100, and 59.8% for smooth muscle actin using immunohistochemistry. Tumor size, tumor rupture, Ki67 index, mitotic index, and postoperative imatinib were independent prognostic factors for small intestinal GISTs.Conclusions:In this study, larger tumor size, high Ki67 index, high mitotic index, the occurrence of tumor rupture, and use of imatinib were independent unfavorable prognostic indicators.

Survival effects of primary and metastatic surgical treatment in metastatic small intestinal tumors: A propensity score-matching study.

ObjectiveTo analyze the effects of primary tumor resection and metastatic lesion resection on the survival of metastatic small intestinal tumors.MethodsThe research subjects were patients with metastatic small bowel tumors identified from 2004 to 2016 in the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching and Kaplan–Meier analyses were performed to analyze the effect of surgery on the prognosis.ResultsA total of 4,034 patients from the SEER database were analyzed. Both before and after the propensity score–matching analysis, the prognosis of patients who underwent primary tumor surgery and metastatic surgery was better than that of patients who did not undergo surgery; all were patients with metastatic small bowel adenocarcinoma (mSIA) or metastatic small intestinal neuroendocrine tumors (mSI-NETs) (all p < .005). Patients with mSIA and adequate lymph node dissection had a longer prognosis than mSIA patients with inadequate lymph node dissection, but this survival benefit was not present in mSI-NET patients. It made no difference in the prognosis of mSIA and mSI-NETs whether localized surgery or intestine-ectomy was performed. Patients with mSIA who underwent primary and metastatic excision plus chemotherapy had the best overall survival and cancer-specific survival rates, whereas mSI-NET patients who underwent primary and metastatic excision had the best overall survival and cancer-specific survival rates (all p < .001).ConclusionIn these carefully selected patients, primary tumor resection and/or metastatic lesion resection significantly improved the survival rates for patients with mSIA and mSI-NETs. The mSIA patients with resectable primary tumors seemed to require a sufficient number of lymph node dissections more than the patients with well-differentiated mSI-NETs.

Incidence and prognosis of patients with small intestinal neuroendocrine tumors in a population based nationwide study

Background & aimsSmall intestinal neuroendocrine tumours (SI-NETs) are the most frequent malignant tumours of the small intestine. Population based studies on SI-NETs are scarce. We aimed to examine the incidence, presentation of disease and prognosis of SI-NET and to determine patient prognosis in those undergoing emergency or elective surgery. MethodsThis was a retrospective population-based study. Information on all patients diagnosed with neuroendocrine tumours of the small intestine (excluding duodenum) from the beginning of the Icelandic Cancer Registry and the pathology departments in the country (1966–2017). Detailed phenotypic information was obtained from medical records on symptoms at diagnosis, treatment, recurrence and survival. ResultsA total of 113 patients with SI-NETs were identified, 3 patients were excluded due to lack of data and/or diagnostic error, leaving 110 patients for final analysis. The incidence of SI-NET was 0.78/100,000 and did not increase during the study period. A total of 42 % (n = 46) of patients were diagnosed incidentally. Long-term prognosis, after a landmark of 12 months, was better in patients who were diagnosed incidentally (HR 0.52; p = 0.03). Overall 89 % (n = 98) of cases underwent surgical resection of the primary tumor, 31 % (n = 30) patients acute or semi-acute surgery and 69 % (n = 68) elective surgery. Emergency surgery was associated with a 6-fold risk of death in the first 12 months after surgery (HR: 5.99; p = 0.01) and associated with more severe surgical complications. However, there was no difference in the long-term risk of death after the first 12 months (HR: 1.39; p = 0.27). ConclusionsThe incidence of SI-NETs has not changed significantly in the last decades. Incidentally diagnosed SI-NET was associated with a favorable long-term prognosis. Emergency surgery in patients with SI-NET was associated with a significantly worse short-term risk of mortality compared to those who underwent elective surgery.

Multiple Small Bowel Intussusceptions Detected by Diagnostic Laparoscopy in an Adult Patient with Previously Undiagnosed Coeliac Disease.

Enteric intussusception in adults is usually associated with the presence of a lead point seen on abdominal computerized tomography. However, as intussusception in coeliac disease may not have a lead point, a surgical procedure is often indicated in order to exclude small bowel tumour. We present the case of a male patient who presented with asymptomatic small bowel intussusception. During exploratory laparoscopy, five enteric intussusceptions were detected and a suspicion for coeliac disease was raised. Postoperative duodenal biopsy and CD3 immunohistochemical staining confirmed the diagnosis of coeliac disease, Marsh type 1.LEARNING POINTSCoeliac disease can present initially with multiple small bowel intussusceptions.Intussusceptions in coeliac disease present without a lead point.In such cases, diagnostic laparoscopy can help to establish the diagnosis.

Abstract 5632: Combinatorial epigenetic targeting of PRC2 complexes upregulates MHC antigen presentation components in melanoma and gastrointestinal cancer cells

Abstract Low tumor immunogenicity is associated with immune escape, immunotherapy resistance, and poor patient survival [1-3]. Major histocompatibility complex (MHC) antigen presentation pathways (APPs) play a crucial role in promoting tumor T-cell recognition and initiating antitumoral immune responses. However, epigenetic silencing of APPs is a common mechanism in various cancers, including melanoma and gastrointestinal malignancies [3,4]. In the current investigation, mouse melanoma (B16/OVA) and human colon cancer (LOVO and HCT116), small intestine cancer (HUTU80), and normal colonic epithelial (CCD841) cell lines were treated with epigenetic drug candidates. As reported [5], a decrease in histone H3K27 methylation marks via polycomb repressive complex 2 (PRC2) inhibitors, as well as altered histone acetylation status from histone deacetylase 3 (HDAC3)-specific inhibition, increased the expression of APP components, based on immunoblotting and RT-qPCR experiments. Normal colonic epithelial cells showed resistance to the treatments, indicating cancer cell-specific effects of the test agents. In B16/OVA cells, flow cytometry and enzyme linked immunosorbent assays corroborated that HDAC3 and/or PRC2 inhibitor combinations increased cell surface occupancy of MHC-I complexes and increased CD8+ T-cell activation. These findings have implications for the clinical application of next-generation combinatorial epigenetic agents [6,7], targeted towards increased tumor immunogenicity and enhanced efficacy of new immunoepigenetic strategies. Supported in part by NCI grant CA122959, by the John S. Dunn Foundation, and by a Chancellor’s Research Initiative.

Abstract 46: Independent clonal origins of synchronous primary tumors in multifocal ileal neuroendocrine tumor patients

Abstract Background: Small intestinal neuroendocrine tumors (SI-NETs) are the most common neoplasms of the small bowel, accounting for 40% of all small intestinal malignancies. Previous high-throughput sequencing studies have shown that SI-NETs have a low somatic mutation rate. Loss of heterozygosity (LOH) at chromosome 18 is the most frequent genomic alteration identified, occurring in ~60% of tumors, and the only recurrent mutations reported to date are loss-of-function mutations in CDKN1B in ~10% of tumors. Most previous studies have focused on sequencing a single primary tumor from each SI-NET patient, even though up to 50% of the patients are diagnosed with multiple synchronous tumors. Thus, the mechanisms by which multifocal SI-NETs arise remain elusive. A better understanding of their tumorigenesis is essential for the optimal treatment of the patients. Materials and Methods: We performed a comprehensive genomic profiling of 75 de-identified synchronous primary tumors, 15 metastases, and 18 normal ileal mucosa and/or whole blood specimens from 13 patients with multifocal ileal NETs using whole genome sequencing. Results: We observed lack of shared somatic variation among the multifocal ileal NET patients and between the synchronous primary tumors within each patient, indicating that these tumors develop independently. Although recurrent copy-number alterations were identified, additional chromosome mapping revealed that tumors from the same patient can gain or lose different parental alleles. In addition to the previously reported CDKN1B loss-of-function mutations, we identified potential driver gene alterations in TNRC6B in a subset of ileal NETs. We also observed two different metastatic dissemination patterns among patients with multiple metastases. Metastases were either clonal or independent, originating from one or several primary tumors. Conclusions: Our study demonstrates notable genomic diversity among multifocal ileal NETs, which corroborates previous literature suggesting that these tumors originate independently. We identified potential loss-of-function mutations in TNRC6B, a candidate tumor suppressor gene in a small subset of ileal NETs. Identification of different metastatic dissemination patterns has an important clinical implication, highlighting the need to carefully remove all synchronous primary tumors of the entire jejunum and ileum at the time of surgery. Lastly, our results indicate that the tumorigenesis of multifocal ileal NETs is not exclusively driven by genomic alterations, suggesting that SI-NETs could be also driven by epigenetic mechanisms, or arise from morphologically normal small intestine as a result of field cancerization. Also, the tumor microenvironment in the ileum may play a role in the growth and development of SI-NETs. Citation Format: NETTA MÄKINEN, Meng Zhou, Zhouwei Zhang, Yosuke Kasai, Elizabeth Perez, Grace E. Kim, Chrissie Thirlwell, Eric Nakakura, Matthew Meyerson. Independent clonal origins of synchronous primary tumors in multifocal ileal neuroendocrine tumor patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 46.

Abstract 6035: Genetically-engineered mouse model for colonic neoplasia presenting mucinous and microsatellite unstable phenotype

Abstract Background and Aim: Mucinous colorectal adenocarcinoma (CRC) is characterized by abundant extracellular mucin which occupies more than 50% of the tumor volume. Mucinous CRCs account for 10% of all CRCs and are likely to be microsatellite unstable including Lynch syndrome. Mucinous CRCs metastasize less frequently. However, once they metastasize, they exhibit resistance to cytotoxic chemotherapeutics, and are associated with poorer prognosis. Although there are some issues to be addressed in mucinous CRCs, mouse models are lacking for mucinous CRCs. Here, we report genetically-engineered mouse models (GEMMs) for mucin-producing colonic tumors with microsatellite instability (MSI), resembling human mucinous CRCs. Method: To induce genetic alterations specifically in colonic epithelial cells, we used CDX2P-G19Cre transgenic mice. In this mouse model, a 9.5-kb fragment in the CDX2 promoter lesion (CDX2P9.5) regulates Cre expression specifically in colonic epithelium (Hinoi et al. Cancer Research 2007). In addition, 19 guanine nucleotides are inserted just after the first ATG, and Cre only expresses in the epithelial cells in which the number of the guanine tract stochastically turns a multiple of three. This mechanism helps our GEMMs to avoid embryonic death due to the genetic events we introduce. We have also reported that tumors in CDX2P9.5-G19Cre;Apcflox/flox mice have an abnormality in two of four MSI markers, suggesting that the tumors are driven by MSI (Sasada et al. PLoS One 2015). TGFBR2 mutation is frequently seen in human MSI CRCs, and inactivation of both Tgfrbr2 and Apc by Villin-Cre results in small intestinal neoplasm producing mucin. Therefore, to test if Tgfbr2 conditional knockout affects the mucin-producing phenotype in the context of MSI-high in this mouse model, we generated CDX2P-G19Cre;Apcflox/+;Tgfbr2flox/flox. Results: In CDX2P-G19Cre; Apcflox/+; Tgfbr2 flox/flox mice, colonic neoplasia developed in 27 out of 40 mice. Approximately 60% of the tumors are well-differentiated adenocarcinoma producing mucin, while the remaining 40% are regular colonic adenomas. In these mucinous adenocarcinomas, tumor cells invade into the muscular layer. We also confirmed the immunoreactivity of β-catenin in cytoplasm and nuclei at the invasive front of the tumors in IHC analysis, indicating that these tumors are driven by abnormal Wnt activity. Nearby to the invasive front, there were mucin that were positive for a PAS reaction. Conclusion: Mucin-producing adenocarcinomas develop in CDX2P9.5-G19Cre;Apcflox/+; Tgfbr2flox/flox mice. This GEMM is a potential mouse model recapitulating human mucinous and microsatellite unstable colorectal adenocarcinoma. The precise mechanism in which mucinous adenocarcinoma develops needs to be elucidated by genomic and transcriptomic analyses. Citation Format: Haruki Sada, Takao Hinoi, Hiroaki Niitsu, Masashi Miguchi, Naoya Sakamoto, Naohide Oue, Hirotaka Tashiro, Hideki Ohdan. Genetically-engineered mouse model for colonic neoplasia presenting mucinous and microsatellite unstable phenotype [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6035.

Abstract 3181: IL-23 knockdown profoundly suppresses intestinal tumorigenesis in APCmin mice

Abstract Colorectal cancer (CRC) is the 3rd most common cancer in the US with an estimated 149,500 new cases and 52,980 deaths in 2021. Studies show that Western-style diet-induced obesity promote CRC by modulating gut inflammatory mediators. We found significant increase in IL-23 levels (p&amp;lt;0.0001) in obese human subjects' plasma (n=15/arm; BMI&amp;gt;30) and its. over expression in colonic tumors (CT) from human and rodent models that highly correlated with, the TCGA gene expression &amp; disease-free survival data. These findings suggested IL-23 as a possible important link between obesity and colon tumorigenesis. The present study was designed to understand the role of IL-23 in colorectal carcinogenesis by using genetic knockout (KO) approach. For this study, Apcmin/+ and IL-23 KO mice were crossbred to generate Apcmin/+ mice with IL-23 in heterozygous or KO conditions. To determine the effect of IL-23 on intestinal tumorigenesis, six-week-old Apcmin/+ mice (N≥15/gender) were grouped by IL-23 genotype i.e., normal (+/+), heterozygous (+/-) and KO (-/-) conditions, then maintained under standard conditions. At 20 weeks of age, all mice were euthanized and intestines were evaluated and compared for tumors incidence and multiplicity. Genetic ablation of IL-23 led to significant suppression of large and small intestinal tumors of APCmin/+ mice in both genders. CT multiplicity of male and female IL-23+/+ Apcmin/+ mice were 1.35±0.16 (Mean±SEM) and 0.61±0.13, respectively. Male and female IL-23+/- Apcmin/+ mice had 77% (0.31+0.15; p&amp;lt;0.0001) and 90% (0.06+0.09; p&amp;lt;0.002) inhibition of CTs, respectively. Interestingly, IL-23 KO led to further suppression in male mice (96% inhibition in male; 0.05+0.05; p&amp;lt;0.0001 and 90% in females; 0.06+0.06; p&amp;lt;0.0001). While IL-23+/+ Apcmin/+ mice was 91% and 52% CT incidence in the male and female mice, respectively. CT incidence was suppressed by 72% (male, p&amp;lt;0.0001) &amp; 88% (female, p&amp;lt;0.005) in the IL-23+/- mice, with further suppression to 95% (male, p&amp;lt;0.0001) &amp; 89% (female, p&amp;lt;0.0025) inhibition in IL-23 KO mice. The strong suppressive effect of IL-23 knockdown was also observed on the small intestinal polyps (SIP) multiplicity. There was a 54% (12.56±1.64; p&amp;lt;0.0001) and 58% (11.45±1.03; p&amp;lt;0.0001) reduction in SIP number in IL23+/- and IL23-/- male Apcmin/+ mice, compared to the IL-23+/+ control mice (27.48±2.38). In female, 55-59% (13.88±1.05 and 12.73±2.03; p&amp;lt;0.0001) less SIP were observed with IL-23 ablation compared to control (30.90±2.54). Apcmin/+ with IL-23 KO showed significant reduction in circulating proinflammatory cytokine and chemokines (Ex: IL-1, IL-10, IL-17, IL-23, CCL-2, CCL-3, CCL-5, TNFa, IFNg) levels compared to IL-23 WT mice. These results clearly demonstrate the colon tumor-promoting role of IL-23 and strengthens our hypothesis to explore this target for CRC prevention in high-risk obese individuals. (Supported in part by P30 CA225520 and Kerley-Cade Endowed Chair) Citation Format: Venkateshwar Madka, Srikanth Chiliveru, Gopal Pathuri, Janani Panneerselvam, Rajani Rai, Nicole C. Stratton, Nandini B. Kumar, Yuting Zhang, Chinthalapally V Rao. IL-23 knockdown profoundly suppresses intestinal tumorigenesis in APCmin mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3181.

Safety and Efficacy of Bevacizumab in Cancer Patients with Inflammatory Bowel Disease.

Simple SummaryIn patients with inflammatory bowel disease, chronic inflammation is a risk factor for the development of digestive and nondigestive cancers. The treatment, as in patients without inflammatory bowel disease, is a combination of chemotherapy and targeted treatments, such as bevacizumab and more recently, immunotherapy. It is generally believed that the use of bevacizumab and chemotherapy could increase toxicity and lead to adverse events in this population. This study aims to evaluate the safety and efficacy of the combination of bevacizumab and chemotherapy in patients with quiescent or moderately active inflammatory bowel disease in various forms of cancer and by increasing the quality of patient care in this subgroup.Background: The safety of bevacizumab in combination with chemotherapy in patients with inflammatory bowel disease (IBD) and digestive and nondigestive cancers is poorly documented. Methods: We retrospectively evaluated patient records of all adult cancer patients with IBD at our institution from April 2007 to May 2016 with an update in November 2019. Results: Twenty-seven patients with a history of IBD (Crohn’s disease, n = 22; ulcerative colitis, n = 5) who were treated with bevacizumab and chemotherapy for metastatic solid tumors were identified. At the time of advanced cancer diagnosis, 18 patients had quiescent IBD, whereas 9 patients had moderately active IBD. Among those with moderately active IBD, five had received corticosteroids less than six months prior to cancer diagnosis and one had received infliximab. The treated cancers were colorectal cancer (n = 13), small bowel cancer (n = 4), non-small cell lung cancer (n = 3), breast cancer (n = 3), and other cancers (n = 4). Patients received bevacizumab in combination with chemotherapy and/or as maintenance for a median of 6.7 months. Grade 2 or higher bevacizumab-related complications were proteinuria in two patients and hypertension, diarrhea, rectal bleeding, and intestinal perforation in one patient each. No clinical IBD flares were observed during bevacizumab treatment. Conclusion: Bevacizumab combined with chemotherapy is safe in cancer patients with moderately active or quiescent IBD.

A multivariate logistic model to predict odds of small bowel cancer by various risk factors.

e16307 Background: Small bowel cancer (SBC) is a rare malignancy, and current epidemiologic literature consists of small single-center studies describing various etiologic associations. Therefore, we evaluated the strength of association of various SBC risk factors using a nationally representative patient sample. Methods: We investigated the National Inpatient Sample 2019 employing International Classification of Diseases-10 (ICD-10) codes to include adult patients with SBC. Odds of SBC were tested for various risk factors individually using univariate logistic regression. In addition, a multivariate regression model was developed to test the odds of developing SBC while controlling for all other risk factors. Analyses were performed using STATA (v 14.2), considering 2 sided P&lt; 0.05 as statistically significant. Results: Out of 30,200,000 adult hospitalized patients in 2019, 9,629 had a diagnosis of SBC. Each one-year increase in age predicted a 4% increased odds of SBC. Males had 28% higher odds compared to females. Compared to whites, Blacks and Asians had higher odds of SBC while Hispanics did not. Smoking, alcohol, HIV, and low socioeconomic status were associated with higher odds of SBC while controlling for all other risk factors ( P &lt; 0.05). Disorders of lipid metabolism, hormone replacement therapy, prior cholecystectomy, celiac disease were associated with lower odds. Crohn’s disease, familial adenomatous polyposis (FAP), and Lynch syndrome were not significantly associated with higher odds of SBC ( P &gt; 0.05). Conclusions: FAP and Lynch syndrome appear to increase the risk of polyp formation in the small intestine but not SBC. The lower odds mentioned for certain variables are merely an association and do not imply a protective effect. The reliance on ICD-10 codes and the inability to distinguish between various cancer subtypes limits our conclusion and needs to be addressed in future studies.[Table: see text]

Landscape of tumor mutation burden and correlation to clinical outcomes in 1,744 solid cancers.

2667 Background: Tumor mutation burden (TMB) has proven clinical utility and efficacy related to immune checkpoint inhibitor (ICI) treatment in different tumor types. However, limited data were available to understand the landscape and matched clinical outcomes to a pan-cancer extent. Methods: Target sequencing results, using TruSight Oncology 500, from 1,744 solid cancer between 2019 and 2021 as a part of real-world clinical practice were collected. Matched clinical and histological outcomes, including PD-L1 expression ( n= 798) and immunotherapy treatment ( n= 400), were analyzed. Results: Among the 33 different cancer types, high TMB was observed in 257 patients (14.7%) with a significantly higher incidence observed in carcinoma of unknown origin (33.3%), bladder cancer (32.3%), and small bowel cancer (30.0%). TMB was positively correlated with the degree of mutation in homologous recombination genes (HRD, 0.76) and microsatellite instability (MSI, 0.51). The predictive value of high TMB to ICI treatment seemed to be enhanced when it was combined with PD-L1 expression, showing higher response rates in the PD-L1 high group (63.3%) than in the low group (22.2%). In the patients with high TMB, both longer overall survival ( p = 0.015) and progression-free survival ( p = 0.020) were observed compared to the patients with low TMB. Conclusions: We examined the landscape of TMB in a different type of cancer using clinical-level target sequencing outcomes. High TMB seems to be a promising predictive biomarker of ICI, showing a positive correlation with alteration in other DNA damage response and repair-related genes and additive value to PD-L1, which needs to be validated through further prospective trials.

P-214 Efficacy and safety of anti-PD-1 agents in patients with dMMR metastatic solid tumours: A retrospective, real-world study

Immune checkpoint inhibitors (ICIs) have been a revolution in the treatment of solid tumours with a significant increase in overall survival rates. High microsatellite instability/mismatch repair deficiency status (MSI-H/dMMR) is considered the first predictive marker of efficacy for ICIs. MSI-H/dMMR, sporadic or hereditary condition, increase tumor immunogenicity with the generation of a high level of neoantigens, suggesting that immunotherapy could be an interesting approach. This condition, more frequently in colorectal cancer, may be present in other tumor types, like endometrial or gastric cancer. The aim of our study is to evaluate the efficacy and safety of treatment with anti-PD-1 agents in patients with dMMR metastatic solid tumours in a single centre. Retrospective study including patients (p) with dMMR tumours treated with ICIs (pembrolizumab or nivolumab) in the University Healthcare Complex of Salamanca from January-2015 to February-2022. Variables related to the patient, the tumour (stage at diagnosis and genotyping of genes involved in dMMR) and treatment (schedules of treatment previously used, maximum response achieved and degree of adverse effects during immunotherapy treatment) were recorded and analyzed. Progression-free survival and overall survival were calculated using the Kaplan-Meier analysis method (SPSS v26). 15p were included. Age (median): 76 years [27-82]. Male: 40%. Tumour distribution: colorectal cancer: 6p, small bowel cancer: 2p, gastric cancer: 2p, endometrial cancer: 2p, breast cancer: 1p, cholangiocarcinoma: 1p and pancreatic cancer: 1p. Stage IV at diagnosis: 5p (33.3%). In all cases we identified alterations in genes involved in the dMMR system: loss of MLH1 and PMS2 expression (53.3%) followed by MSH2 (-) and MSH6 (-) deficiency (26.7%). In 4p (26.7%) immunotherapy was used as first line of treatment for metastatic disease. In 11p (73.3%) immunotherapy was initiated after progression to at least 1 prior chemotherapy treatment. In terms of treatment efficacy: 10p (66.7%) had disease control defined as complete response; 3p (20%), partial response; 3p (20%) or stable disease; 4p (26.7%). Median progression-free survival was 7.23 months (95% CI, 0.0-19-36). With a median follow-up of 15 months, median overall survival had not been reached at the time of analysis. Treatment-related adverse events were identified in 9p (60%): pneumonitis, alterations in liver function and hepatitis, skin alterations, hypothyroidism, myalgia or asthenia. In 2 of them (13.3%) had grade 3-4 toxicity and led to definitive discontinuation of treatment. Our findings confirm previous evidence. Immune checkpoint inhibitors are shown as a hopeful option in the dMMR tumours approach. They have an adequate safety profile with mostly mild immuno-related toxicity, although close monitoring and management of possible serious adverse effects is necessary.

The incidence and comparative prognosis of primary cancers with metastasis to non-common sites: A SEER database analysis of 2016-2018.

e22506 Background: Primary tumors can present late with metastasis to uncommon sites (such as adrenals, bone marrow, pleura, malignant pleural effusion, peritoneum, and skin, among others) as well as common sites (such as liver, bone, lung, and distal lymph nodes). Our study aimed to investigate the characteristics and comparative survival for metastasis to uncommon sites at the time of diagnosis using the Surveillance, Epidemiology, and End Results (SEER) database. Methods: We extracted the data from the SEER database for the years 2016-2018 to include all patients presenting with metastasis to uncommon sites at diagnosis without restrictions on age, race, year of diagnosis, or histological type. Uncommon sites of metastasis were coded as other sites in the SEER database and did not involve liver, bone, brain, lung, and distal lymph nodes. We used R software to perform the descriptive analysis for uncommon sites according to the primary sites and co-metastasis along with their survival. Results: A total of 25,345 patients were included with metastasis to uncommon sites with a female predominance of 13,033 (51.4 %); the mean age at diagnosis was 68 ± 17 years. Lung and bronchus primaries represented the largest proportion with metastasized to uncommon sites 10,612 (41.9%), followed by non-Hodgkin's lymphoma-nodal 1,871 (7.4%), pancreas 1,690 (6.6%), stomach 940 (3.7%), and ovarian 885 (3.4%). The incidence was most common in respiratory cancers in ages 61-80 years (25%) and least in breast primaries in ages 18-40 years (0.1%). Whites compared to other races had a higher incidence. Liver cancer had the worst prognosis with a median survival of 1 month, whereas small intestine tumors were associated with a better prognosis with a median survival of 13 months. Further survival data is mentioned in the table. Conclusions: Our study concluded that the lung and bronchus cancers were the most common primaries metastasized to uncommon sites at diagnosis while the liver had the worst survival. These findings will help redirect the available screening tools to improve survival in patients with primary tumors with metastasis at diagnosis and may also play an essential role in future research and achieve a better prognosis for cancer patients.[Table: see text]

Does the primary tumor origin affect the prognosis of patients with gastrointestinal malignancies and peritoneal carcinomatosis?

e16223 Background: Multiple gastrointestinal malignancies have the potential to metastasize in the peritoneal cavity. Peritoneal carcinomatosis (PC) is often associated with disease progression and poor prognosis. However, there has been limited data on the impact of tumor origin on the survival outcomes in patients with PC. We sought to examine the differences in the cancer-specific survival of gastrointestinal malignancies with PC. Methods: We performed a retrospective study of patients ≥18 years of age diagnosed with gastrointestinal malignancies (stomach, colorectal, small intestine, appendix) with PC between 2010-2016 using data extracted from the United States Surveillance, Epidemiology, and End Results (SEER) database. The study endpoint was cancer-specific mortality (CSM). We used the Kaplan-Meier method to evaluate the cancer-specific survival for each primary tumor. Cox proportional hazard regression analysis was used to examine the association between CSM and other patient characteristics. The effects were expressed as hazard ratios (HR) and 95% confidence intervals (CI). Results: We identified 7374 patients who met the inclusion criteria; 2797 (37.9%) with stomach cancer, 3274 (44.4%) with colorectal cancer, 703 (9.5%) with small intestine cancer, and 600 (8.1%) with appendiceal cancer. The median age at diagnosis was 64 (Interquartile Range (IQR), 53-75). Median follow-up was 11 months (IQR 3-22). 3709 patients (50.3%) were female. The majority was White (76.2%). 3942 (53.5%) were married. 5679 (77.0%) were insured. 4343 (58.9%) received chemotherapy and 3682 (49.9%) received surgery. Compared to PC of appendiceal cancer primary, stomach cancer primary had an increased risk of CSM (HR = 4.89; 95% CI 4.23-5.65), followed by colorectal cancer (HR = 2.78, 95% CI 2.41-3.21), and small intestine (HR = 1.17; 95% CI 0.98-1.41). Across all patients, surgery and chemotherapy were associated with a lower risk of CSM. Conclusions: Primary tumor origin significantly affects outcomes of gastrointestinal malignancies with PC. Surgery and chemotherapy were associated with decreased CSM. [Table: see text]

Prevalence and survival of gastrointestinal malignancies with brain metastasis: Surveillance, Epidemiology, and End Results SEER database analysis 2010-2018.

e14004 Background: Gastrointestinal (GI) cancers are amongst the leading causes of cancer-related death worldwide. GI cancers with brain metastasis on presentation are rare; however, the oncologist will intermittently encounter such patients. Unfortunately, there is a paucity of data to inform the prevalence and prognosis of GI cancers with brain metastasis, especially in light of therapeutic developments in the past decade and whether that might have influenced the survival. In this study, we measured the prevalence of brain metastasis secondary to primary GI malignancies at the time of diagnosis, the observed median survival, and Kaplan-Meier 2-years overall survival. The aim is to highlight the burden and prognosis of this population. Methods: We queried the Surveillance, Epidemiology, and End Results (SEER) Program 18 registry (2010-2018) database. We identified the total number of patients and patients with brain metastasis at the time of diagnosis for the following gastrointestinal cancers: esophagus, stomach, pancreas, colon, rectum, liver, intrahepatic biliary duct, and gallbladder. We obtained the prevalence, the observed median survival, and the 2-years survival using the Kaplan-Meier method. Results: The total number of cases, prevalence, median survival, and 2-years overall survival are shown in the table. The prevalence of brain metastasis at diagnosis was highest for esophageal cancer at 1.41%, followed by stomach 0.52%, and gall bladder 0.37%. The lowest incidence was small intestinal cancers at 0.13%. The median survival was short, ranging between 2 to 4 months for all studied cancers except for the small intestine and rectum at about six months. Kaplan-Meier 2-years survival was highest for the small intestine at 17%, and the worst was gallbladder, where no one survived at the end of the 24 months. Conclusions: Brain metastasis at the time of diagnosis of GI cancer remains rare. However, its presence portends an abysmal prognosis of 2-4 months. This study helps to inform the practicing oncologist of the current prevalence and prognosis of GI malignancies with brain metastasis on presentation. In addition, these findings encourage prompt involvement of palliative care, setting realistic expectations, and discussing goals of care once such a grave diagnosis is made.[Table: see text]

National claims data analysis of outcomes of hospitalized cancer patients without COVID-19 infection during versus prior to the COVID-19 pandemic.

e18679 Background: There has been growing concern regarding the impact of the COVID-19 pandemic on health care delivery and disruption of care to cancer patients. Reductions in cancer surgeries, delays in administration of life saving chemo and radiation therapies, and lower rates of cancer-related hospitalizations have been reported. While cancer patients with COVID-19 infection have poor hospitalization outcomes, less is known about the outcomes of hospitalized cancer patients without the infection. This study aimed to describe the impact of the COVID-19 pandemic on outcomes of the most common cancer-related hospital admissions for patients without COVID-19 infection at a national level using insurance claims. Given the concern for disruptions in their care, we hypothesized that hospitalized cancer patients may have worse outcomes. Methods: We used the Optum Clinformatics Data Mart, consisting of claims records linked to electronic health records, including an average of 8 million adult Americans per year enrolled for at least 6 months. We identified cancer-related hospitalizations from 02/2018-05/2021 and included patients with at least of one of these cancer types: breast, prostate, bladder, ovarian, cervical, lung, colorectal, esophageal, liver, small intestine, gastric, or gallbladder cancer. Patients with cancer-related hospitalization who had COVID-19 infection were excluded. The main outcome was “severe adverse outcome” and included at least one of the following: mortality during or within 30 days of hospitalization, mechanical ventilation during hospitalization, intensive care unit admission, or discharge to hospice. We used Poisson regression to compare the number of hospitalizations before (2/1/2018-1/30/2020) and during (2/1/2020-5/30/2021) the pandemic and a Chi-squared test to compare the proportion of cancer-related hospitalizations with severe adverse outcomes over that time period in 4-month intervals and across cancer types, gender, (male vs female) and geography (the 9 Census Bureau regions). Results: There were 82,796 cancer-related hospitalizations in the period 2/2018-05/2021. A slightly higher proportion of cancer-related hospitalizations resulted in a severe adverse outcome during the pandemic as compared to prior to the pandemic (41.8% vs 40.9%; p = 0.012). There were no differences by cancer site, gender, or geography. The number of hospitalizations was lower during vs prior to the pandemic (p &lt; 0.0001). Conclusions: The number of cancer-related hospitalizations during the pandemic was lower compared to before the, and a slightly higher proportion of those hospitalized experienced severe adverse outcomes among insured U.S. cancer patients without COVID-19 infection. The lower number of cancer-related hospitalizations during the pandemic warrants further investigation.

A Canadian single-centre experience with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for abdominal malignancies.

Background:Cytoreductive surgery in combination with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) has recently shown promise for the treatment of patients with various types of peritoneal carcinomatosis (PC). However, it is an extensive procedure that is associated with a variety of morbidities. We evaluated the safety and clinical outcomes of CRS-HIPEC performed at our centre.Methods:Patients with abdominal malignancies who underwent CRS-HIPEC between February 2005 and December 2018 at the Centre hospitalier de l’Université de Montréal (CHUM) were retrospectively reviewed.Results:A total of 141 patients were identified (66 with appendiceal cancer, 62 with colorectal cancer, 10 with mesothelioma and 3 with small intestinal tumours). The median age was 55 years. Median overall survival (OS) was not reached for patients with appendiceal tumours; it was 38.3 months for colorectal cancers. Among patients with colorectal cancer, survival was significantly better for those who received intraperitoneal HIPEC with oxaliplatin (74.9 mo) compared with mitomycin C (29.1 mo) (p = 0.006). Complete cytoreductive surgery and low peritoneal carcinomatosis index were associated with the highest overall survival in patients with appendiceal tumours and those with colorectal tumours.Conclusion:CRS-HIPEC can be performed with acceptable morbidity in patients with PC. These results validate the outcomes of previously reported trials, but further prospective trials are warranted to determine which patients will most benefit from the addition of HIPEC to CRS.

Development of a Deep Learning Model for Malignant Small Bowel Tumors Survival: A SEER-Based Study.

Background This study aims to explore a deep learning (DL) algorithm for developing a prognostic model and perform survival analyses in SBT patients. Methods The demographic and clinical features of patients with SBTs were extracted from the Surveillance, Epidemiology and End Results (SEER) database. We randomly split the samples into the training set and the validation set at 7:3. Cox proportional hazards (Cox-PH) analysis and the DeepSurv algorithm were used to develop models. The performance of the Cox-PH and DeepSurv models was evaluated using receiver operating characteristic curves, calibration curves, C-statistics and decision-curve analysis (DCA). A Kaplan–Meier (K–M) survival analysis was performed for further explanation on prognostic effect of the Cox-PH model. Results The multivariate analysis demonstrated that seven variables were associated with cancer-specific survival (CSS) (all p < 0.05). The DeepSurv model showed better performance than the Cox-PH model (C-index: 0.871 vs. 0.866). The calibration curves and DCA revealed that the two models had good discrimination and calibration. Moreover, patients with ileac malignancy and N2 stage disease were not responding to surgery according to the K–M analysis. Conclusions This study reported a DeepSurv model that performed well in CSS in SBT patients. It might offer insights into future research to explore more DL algorithms in cohort studies.