Presence Of Peritoneal Metastases Research Articles

Clinical outcomes and biomarker exploration of first-line PD-1 inhibitors plus chemotherapy in patients with low PD-L1-expressing of gastric or gastroesophageal junction adenocarcinoma

BackgroundThe beneficial effects of first-line programmed death-1 (PD-1) inhibitors plus chemotherapy in patients with low programmed death-ligand 1 (PD-L1)-expressing advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma are controversial.MethodsWe conducted a retrospective analysis of patients with G/GEJ adenocarcinoma who had undergone first-line treatment with PD-1 inhibitors plus chemotherapy between October 2017 and May 2022. The primary outcomes were objective response rate (ORR) and progression-free survival (PFS). SPSS software V27.0 was used for data analysis.ResultsOf 345 enrolled patients, 290 had measurable lesions. The overall ORR was 59.3%. PD-L1 status was available in 171 patients, and 67.8% of them were considered as low PD-L1 expression level (combined positive score (CPS) < 5). Patients with PD-L1 CPS < 5 showed a lower response rate (51.1% vs 70.8%, P = 0.024) and a worse PFS (P = 0.009) compared to those with PD-L1 CPS ≥ 5. In the PD-L1 low-expression cohort, patients with non-diffuse type, GEJ cancer, synchronous metastasis, distant lymph node metastasis, liver metastasis, non-peritoneal metastasis, and HER2 positive were significantly associated with higher response rates to PD-1 inhibitors plus chemotherapy (P < 0.05). The presence of peritoneal metastasis (P = 0.028) and diffuse type (P = 0.046) were identified as independent predictors of poor PFS in multivariate analysis of the PD-L1 CPS < 5 subgroup. When evaluated for correlation with overall survival (OS) in the PD-L1 low-expression subgroup, peritoneal metastasis was found to be the only independent prognostic factor of an increased risk of death (hazard ratio: 2.31, 95% CI 1.09–4.90; P = 0.029).ConclusionsPD-L1 CPS ≥ 5 is significantly associated with improved response and extended PFS in G/GEJ cancer patients treated with a combination of PD-1 inhibitors and chemotherapy. Specific subgroups within the low PD-L1-expressing population, such as those with non-diffuse-type tumors and without peritoneal metastases, may also benefit from immunotherapy combined with chemotherapy.

Value of Surgical Cytoreduction in Patients with Small Intestinal Neuroendocrine Tumors Metastatic to the Liver and Peritoneum.

Cytoreductive hepatectomy can improve survival and symptoms of hormonal excess in patients with small intestinal neuroendocrine tumor (siNET) liver metastases, but whether to proceed when peritoneal metastases are encountered at the time of planned cytoreductive hepatectomy is controversial. This was a retrospective review of patients who underwent surgical management of metastatic siNETs at Mayo Clinic between 2000 and 2020. Patients who underwent cytoreductive operation for isolated liver metastases or both liver and peritoneal metastases were compared. Of 261 patients who underwent cytoreductive operation for siNETs, 211 had isolated liver metastases and 50 had liver and peritoneal metastases. Complete cytoreduction was achieved in 78% of patients with isolated liver metastases and 56% of those with liver and peritoneal metastases (p = 0.002). After complete cytoreduction, median overall survival (OS) was 11.5 years for isolated liver metastases and 11.2 years for liver and peritoneal metastases (p = 0.10), and relief of carcinoid syndrome was ≥ 97% in both groups. After incomplete cytoreduction with debulking of > 90% of hepatic disease and/or closing Lyon score of 1-2, median OS was 6.4 years for isolated liver metastases and 7.1years for liver and peritoneal metastases (p = 0.12). Patients with siNETs metastatic to both the liver and peritoneum have favorable outcomes after aggressive surgical cytoreduction, with the best outcomes observed after complete cytoreduction. Therefore, the presence of peritoneal metastases should not by itself preclude surgical cytoreduction in this population.

Peritoneal metastases in patients with neuroendocrine neoplasms: a challenging site of metastases with clinical and prognostic implications.

Peritoneal metastases (PM) of neuroendocrine neoplasm (NEN) origin are identified with increasing frequency and exert a significant effect on quality of life and clinical status of the patients. The aim of this study was to identify the characteristics and the prognostic significance of PM in patients with NENs. A retrospective analysis of the data of patients from two tertiary referral centers was performed. We defined a control group of age- and gender-matched NEN patients with comparable stage IV disease but no PM. We analysed 70 patients (41 females) with PM. Small intestine was the most common primary NEN site (87.1%). PM prevalence was 10.3%. Forty-four patients presented with synchronous PM, whereas 26 developed metachronous PM. The majority of patients had other concomitant metastases (50 hepatic, 6 lung and 12 bone metastases). Twelve patients developed intestinal obstruction. After PM diagnosis, 76% of patients received treatment with somatostatin analogues while six patients (8.6%) were treated with peptide receptor radionuclide therapy (PRRT). The median progression-free survival (PFS) in the PRRT-treated group was 15months (95% CI 2-28). Median overall survival (OS) in the PM group was 142months [95% CI 71-213] while it was not reached in the control group. Peritoneal metastases show low prevalence among NEN patients and are most likely to develop in patients with small intestinal NENs and advanced metastatic disease. The presence of PM does seem to be associated with a negative prognostic impact on OS of NEN patients and their identification and prompt treatment is of major importance.

Genomic Characterization and Clinical Outcomes of Patients with Peritoneal Metastases from the AACR GENIE Biopharma Collaborative Colorectal Cancer Registry.

Utilizing the GENIE BPC registry, this study found that PM in patients with colorectal cancer occur more frequently in females and right-sided primary tumors and are associated with worse OS. In addition, we found a lower frequency of APC alterations and a higher frequency in MED12 alterations in patients with PM.

Real-world comparison of treatment outcomes between advanced esophagogastric junction adenocarcinoma and gastric adenocarcinoma.

267 Background: The characteristics of esophagogastric junction adenocarcinoma (EGJA) differ from those of gastric adenocarcinoma (GA). Although chemotherapy for advanced GA has been adapted for advanced EGJA, its efficacy remains unknown. This study aims to elucidate the effectiveness of chemotherapy for advanced EGJA in real-world practice. Methods: This retrospective study compared treatment outcomes between advanced GA and EGJA in patients with performance status (PS) 0 to 2 who received doublet or triplet chemotherapy, including platinum agents, as first-line treatment at our hospital between 2010 and 2020. Patients with non-curative resection factors limited to positive peritoneal cytology, or those who relapsed during adjuvant chemotherapy or within 6 months after its completion, were excluded. Results: Out of the total 825 patients, 765 had GA and 60 had EGJA. The baseline characteristics of the GA and EGJA groups were as follows, respectively: median age 65.0 and 59.5 years (p = 0.02); PS 0, 35.9% and 33.3%; PS 1, 57.5% and 65.0%; PS 2, 6.5% and 1.7% (p = 0.28); HER2 positive, 16.1% and 26.7% (p = 0.06); diffuse histology, 52.7% and 26.7% (p &lt; 0.01); lymph node metastasis, 74.0% and 93.3% (p &lt; 0.01); peritoneal metastasis, 66.4% and 25.0% (p &lt; 0.01); liver metastasis, 26.4% and 40.0% (p = 0.03); lung metastasis, 6.5% and 16.7% (p &lt; 0.01). The proportions of fluoropyrimidine, taxanes, and irinotecan in all treatment lines did not differ between the two groups (fluoropyrimidine, 99.7% vs. 100%; taxanes, 70.1% vs. 73.3%; irinotecan, 23.0% vs. 23.3%). However, the EGJA group used ramucirumab, trastuzumab, and immune checkpoint inhibitors (ICIs) significantly more frequently than the GA group (ramucirumab, 27.8% vs. 43.3%, p = 0.02; trastuzumab, 15.4% vs. 26.7%, p = 0.03; ICIs, 21.0% vs. 41.7%, p &lt; 0.01). Overall survival did not differ between the two groups (median, 14.8 months vs. 18.5 months, HR 0.80; 95% CI, 0.59-1.10, p = 0.17). Moreover, multivariate analysis revealed that EGJA and GA had a comparable prognosis (HR 1.23; 95% CI, 0.87-1.72, p = 0.24). HER2 positivity was a favorable prognostic factor in multivariate analysis, whereas diffuse histology, poor PS, lymph node metastasis, liver metastasis, and the presence of peritoneal metastasis were poor prognostic factors. There was no difference in time-to-treatment failure between the two groups for first-line (median, 6.1 vs. 4.9 months, HR 0.96; 95% CI, 0.73-1.28, p = 0.80), second-line (median, 2.9 vs. 3.5 months, HR 0.99; 95% CI, 0.73-1.34, p = 0.93), and third-line treatment (median, 1.9 vs. 2.7 months, HR 0.78; 95% CI, 0.53-1.13, p = 0.62). Conclusions: In real-world practice, the efficacy of chemotherapy for advanced EGJA was comparable to that for advanced GA.

Comparing Characteristics of Pelvic High-grade Serous Carcinomas with and without Breast Cancer Gene Variants on MR Imaging.

To compare MRI findings of high-grade serous carcinoma (HGSC) with and without breast cancer (BRCA) gene variants to explore the feasibility of MRI as a genetic predictor. We retrospectively reviewed MRI data from 16 patients with BRCA variant-positive (11 patients of BRCA1 and 5 patients of BRCA2 variant-positive) and 32 patients with BRCA variant-negative HGSCs and evaluated tumor size, appearance, nature of solid components, apparent diffusion coefficient (ADC) value, time-intensity curve, several dynamic contrast-enhanced curve descriptors, and nature of peritoneal metastasis. Age, primary site, tumor stage, bilaterality, presence of lymph node metastasis, presence of peritoneal metastasis, and tumor markers were also compared between the groups with the Mann-Whitney U and chi-square tests. The mean tumor size of BRCA variant-positive HGSCs was 9.6 cm, and that of variant-negative HGSCs was 6.8 cm, with no significant difference (P = 0.241). No significant difference was found between BRCA variant-positive and negative HGSCs in other evaluated factors, except for age (mean age, 53 years old; range, 32-78 years old for BRCA variant-positive and mean age, 61 years old; range, 44-80 years old for BRCA variant-negative, P = 0.033). Comparing BRCA1 variant-positive and BRCA2 variant-positive HGSCs, BRCA1 variant-positive HGSCs were larger (P = 0.040), had greater Max enhancement (P = 0.013), Area under the curve (P = 0.013), and CA125 (P = 0.038), and had a higher frequency of lymph node metastasis (P = 0.049), with significance. There was no significant difference in the MRI findings between patients with HGSCs with and without BRCA variants. Although studied in small numbers, BRCA1 variant-positive HGSCs were larger and more enhanced than BRCA2 variant-positive HGSCs with higher CA125 and more frequent lymph node metastases, and may represent more aggressive features.

Colorectal Peritoneal Metastases State of Art

The presence of peritoneal metastasis (PM) in patients with colorectal cancer (CRC) is associated with an extremely poor prognosis. Recent developments in the field of treatment including new drugs, translational research for new molecules offer a future plan to achieved improved of Survival. On the other hand, numerous clinical trials regarding the role of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy have now opened new doors in peritoneal metastasis treatment. This review presents all the controversial data and options regarding this approach.

Low Expectancy of Conversion Surgery with R0 Resection in Patients with CEA > 5.0 ng/mL at the Initial RECIST Evaluation for Metastatic Gastric Cancer.

This retrospective study examined early the predictive factors for successful conversion surgery (CS) with R0 resection in patients with metastatic gastric cancer (MGC) who underwent systemic chemotherapy. This study included 204 patients diagnosed with metastatic gastric adenocarcinoma, who received chemotherapy between 2009 and 2019. Of these patients, 31 (15%) underwent CS with R0 resection. The incidence of CS with R0 resection was not affected by the volume of metastatic lesions or the presence of peritoneal metastasis. The overall survival time of the CS with R0 resection group was significantly longer than that of the non-CS group (hazard ratio, 0.12; 95% confidence interval, 0.07-0.23; p < 0.0001), with a 5 year overall survival rate of 50.2%. Multivariate analysis of 150 patients, excluding those with disease progression until the initial Response Evaluation Criteria in Solid Tumors (RECIST) evaluation, showed that carcinoembryonic antigen > 5.0 ng/mL at the initial RECIST evaluation was an independent, significant, and unfavorable predictor of CS with R0 resection (odds ratio, 0.21; p = 0.0108), whereas systemic chemotherapy with trastuzumab for HER2-positive cancer was a favorable factor (odds ratio, 4.20; p = 0.0119). Monitoring serum carcinoembryonic antigen levels during chemotherapy may be a useful predictor of the CS implementation in patients with MGC.

Diagnostic Accuracy of Abdominal CT for Locally Advanced Colon Tumors: Can We Really Entrust Certain Decisions to the Reliability of CT?

Many different options of neoadjuvant treatments for advanced colon cancer are emerging. An accurate preoperative staging is crucial to select the most appropriate treatment option. A retrospective study was carried out on a national series of operated patients with T4 tumors. Considering the anatomo-pathological analysis of the surgical specimen as the gold standard, a diagnostic accuracy study was carried out on the variables T and N staging and the presence of peritoneal metastases (M1c). The parameters calculated were sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios, as well as the overall accuracy. A total of 50 centers participated in the study in which 1950 patients were analyzed. The sensitivity of CT for correct staging of T4 colon tumors was 57%. Regarding N staging, the overall accuracy was 63%, with a sensitivity of 64% and a specificity of 62%; however, the positive and negative likelihood ratios were 1.7 and 0.58, respectively. For the diagnosis of peritoneal metastases, the accuracy was 94.8%, with a sensitivity of 40% and specificity of 98%; in the case of peritoneal metastases, the positive and negative likelihood ratios were 24.4 and 0.61, respectively. The diagnostic accuracy of CT in the setting of advanced colon cancer still has some shortcomings for accurate diagnosis of stage T4, correct classification of lymph nodes, and preoperative detection of peritoneal metastases.

The prognostic role of neutrophil/lymphocyte ratio and monocyte/lymphocyte ratio in advanced stage gastric cancer patients receiving chemotherapy: a single center experience

Objective: Several studies revealed that peripheral blood Neutrophil/Lymphocyte ratio (NLR) and Monocyte/Lymphocyte Ratio (MLR) were prognostic in various cancer types. However, there are no excessive information about the prognostic significance of NLR and MLR in patients with advanced gastric cancer. As a result, we examined whether NLR and/or MLR could be used as a prognostic marker to predict survival outcomes in patients with advanced gastric cancer receiving palliative chemotherapy.&#x0D; &#x0D; Method: We retrospectively analyzed 119 patients with gastric cancer receiving chemotherapy. We evaluated the relationship between potential prognostic factors and overall survival (OS) times using the Kaplan-Meier method and Cox regression survival modelling.&#x0D; &#x0D; Results: The median overall survival of the patients was 6.9 (2.1-41.6) months. In univariate analysis, NLR (p&lt; 0.001), ECOG performance status (p&lt; 0.001), presence of liver metastases (p&lt; 0.001) and presence of peritoneal metastases (p&lt; 0.001) were found to be associated with survival. The multivariate survival model showed the high NLR (HR=1.59, 95% CI 1.6-2.40, p= 0.026), the patients with ECOG performance score 2-3 (HR=2.91, 95% CI 1.60-5.27, p

Role of Circulating Tumor DNA Among Patients with Colorectal Peritoneal Metastases.

This was a review of circulating tumor DNA (ctDNA) in patients with peritoneal metastases from colorectal cancer. We searched the PubMed database for studies reporting detection of ctDNA in patients with colorectal cancer (CRC) and with peritoneal metastases (PM) from colorectal cancer (CRPM). We extracted data on the population included, number of subjects, study design, type of ctDNA assay used and schedule, and the major findings from these publications. We identified 13 studies for review investigating ctDNA, using a variety of ctDNA assays, among 1787 patients with CRC without PM, as well as four eligible published and one unpublished (in press) studies, which included 255 patients with PM from any primary site and 61 patients with CRPM. Among the 13 studies investigating ctDNA among CRC without PM, posttreatment surveillance ctDNA was associated with recurrence and was generally more sensitive than imaging or tumor markers. Among the five studies including patients with PM, ctDNA was not universally able to detect the presence of PM, but when present, ctDNA predicted worse outcomes. Circulating-tumor DNA is a potentially useful surveillance tool for patients with CRC. However, the sensitivity of ctDNA to detect CRPM is variable and warrants further inquiry.

Clinical value of preoperative serum tumor markers CEA, CA19-9, CA125, and CA15-3 in surgically treated urachal cancer.

Urachal adenocarcinoma (UrAC) is a very rare malignancy with a poor prognosis. The role of preoperative serum tumor markers (STMs) in UrAC is unknown. The aim of this study was to assess the clinical value of elevated STMs including carcinoembryonic antigen (CEA), cancer antigen 19-9 (CA19-9), cancer antigen 125 (CA125), and cancer antigen 15-3 (CA15-3) in surgically treated UrAC, and to evaluate their prognostic significance. This was a retrospective study of consecutive patients with histopathologically confirmed UrAC who underwent surgical treatment at a single tertiary hospital. Blood levels of CEA, CA19-9, CA125, and CA15-3 were determined before surgery. The proportion of patients with elevated STMs was calculated, as well as the association between elevated STMs and clinicopathological characteristics, recurrence-free survival and disease-specific survival. Of the 50 patients included; CEA, CA 19-9, CA125, and CA15-3 were elevated in 40%, 25%, 26%, and 6% respectively. Elevated CEA was associated with higher pT-stage (odds ratio [OR] 3.3 [95% confidence interval 1.0-11.1], P = 0.003), higher Sheldon stage (OR 6.9 [95% CI 0.8-60.4], P = 0.01), male sex (OR 4.7 [95% CI 1.2-18.3], P = 0.01), and the presence of peritoneal metastases at the time of diagnosis (OR 3.5 [95% CI 0.9-14.2], P = 0.04). Elevated CA19-9 was associated with signet-cell component (OR 1.7 [95% CI 0.9-3.3], P = 0.03) and elevated CA125 was associated with peritoneal metastases at the time of diagnosis (OR 6.0 [95% CI 1.2-30.6], P = 0.04). Elevated STMs before surgery were not associated with recurrence-free survival and/or disease-specific survival. A subset of patients with surgically treated UrAC has elevated STMs preoperatively. CEA was most frequently (40%) elevated and correlated with unfavorable tumor characteristics. However, STM levels did not correlate with prognostic outcomes.

Prognostic impact of depth of response (DpR) and early tumour shrinkage (ETS) in patients (pts) with BRAF V600E mutated (mut) metastatic colorectal cancer (mCRC) receiving targeted therapy (TT) as second-line treatment.

3568 Background: Encorafenib and cetuximab (EC) is the standard of care for pre-treated patients (pts) with BRAF V600E mut mCRC. DpR and ETS previously showed a strong correlation with survival outcomes in mCRC pts receiving 1st-line therapy. We assessed these tumour dynamic response parameters and their association with clinical outcome in pts with BRAF V600E mut mCRC treated with TT in second-line. Methods: Patients treated in a real-life setting with EC or EC plus binimetinib (ECB) in 20 Italian centres were included. Pts with measurable disease and at least one available disease reassessment by CT scan were eligible. Pts experiencing disease progression as best response (i.e. primary resistant) were not evaluable for DpR and ETS. Associations between DpR and ETS and progression free survival (PFS) and overall survival (OS) were tested by univariate and multivariate models. Results: 105 pts were included: 89 (85%) and 16 (15%) pts were treated with EC and ECB, respectively. Median PFS and OS were 5.2 and 10.3 mos, respectively. Twenty-nine pts (28%) were primary resistant, while 76 (72%) pts achieved disease control (51 [48%] and 25 [24%] pts had SD or CR/PR, respectively). Among baseline characteristics, the presence of peritoneal metastases was a predictor of primary resistance (p = 0.04). Among pts evaluable for response parameters (n = 76), median DpR was 15% and ETS occurred in 28 pts (37%). Mucinous histology was associated with a significantly lower magnitude of DpR (p = 0.005) and a lower rate of ETS (p = 0.002). A significant association between DpR and PFS was observed, both as a dichotomous ( ie, ≥ or &lt; median value) and continuous variable in univariate and multivariate analyses. Also RECIST response correlated with PFS in the two models (table). DpR was associated with OS in the univariate analyses, but this was not confirmed in the multivariate models (table). No correlation between ETS and survival, either as a dichotomous ( ie, ≥ or &lt; 20%) or a continuous variable, was observed. Conclusions: Having a DpR of at least 15% predicts longer PFS and OS in patients with BRAF V600E mut mCRC receiving TT as second-line treatment. An independent cohort of pts treated with second-line chemotherapy +/- antiangiogenic is under investigation as control group. [Table: see text]

Malignant ascites as a marker of peritoneal carcinomatosis burden in patients with colorectal and gastroesophageal cancer.

455 Background: Malignant ascites occurs frequently in patients with gastric cancer (GC) and colorectal cancer (CRC) with peritoneal metastasis (PM). The presence of PM and malignant ascites have been independently reported to confer resistance to systemic therapy and poorer prognosis. However, the occurrence of malignant ascites as a function of increasing peritoneal carcinomatosis burden has been less studied and reported. Methods: We reviewed prospective cohorts of gastric cancer and colorectal cancer patients with PM. The first cohort was a prospective group of GCPM patients receiving bi-directional systemic and peritoneal-directed therapies (catheter-based intraperitoneal chemotherapy and/or pressurized intraperitoneal aerosol chemotherapy respectively) at a tertiary oncology center in Singapore. Clinico-pathological data, including Peritoneal Cancer Index (PCI) and the presence or absence of ascites based on diagnostic laparoscopy, was collected. To orthogonally validate the hypothesis of malignant ascites as a function of peritoneal carcinomatosis burden in gastrointestinal malignancies, we studied the relationship between ascites, PM and survival in an independent cohort of metastatic CRC patients eligible for first-line systemic treatment enrolled in two randomized clinical trials in different Italian cancer centers. Results: In the first cohort of 82 patients with GCPM, the median PCI was 19 (inter-quartile range (IQR) 8 – 26) in the group with ascites and 3 (IQR 1 – 12) in the group without ascites (p=0.005), suggesting ascites occurs with higher PM burden. The median overall survival (OS) was poorer in patients with ascites (13.4 vs 16.4 months, HR 1.6, 95% CI 0.9 – 2.8, p=0.082). The median OS in patients with PCI of &lt;7 was 17.3 months (95% 12.0 – 22.7) and 13.8 months (95% CI 11.0 – 16.6) in those with PCI score &gt;7. In the validation cohort of 900 CRC patients, presence of malignant ascites and PM resulted in poorer survival compared to patients with PM and no malignant ascites (HR for OS PM with ascites vs PM without ascites 2.01 (95% CI 1.37 - 2.96), p&lt;0.001). Interestingly, those with PM and ascites had a poorer survival to those with stage IV disease without peritoneal involvement, while those with PM without ascites did not have a statistically significant difference (PM with malignant ascites vs. no peritoneal disease, HR for OS 2.14, 95% CI 1.57 – 3.01, p=0.007; PM without ascites vs no peritoneal disease, HR for OS 1.10, 95% CI 0.91 – 1.34). Conclusions: Our study of patients with colorectal or gastric cancer and peritoneal metastases suggest the presence of malignant ascites as a function of increased peritoneal carcinomatosis burden among patients with metastatic gastrointestinal malignancies, with correspondingly poorer survival outcomes.

Complex molecular profile of DNA repair genes in epithelial ovarian carcinoma patients with different sensitivity to platinum-based therapy.

Epithelial ovarian carcinoma (EOC) is known for high mortality due to diagnosis at advanced stages and frequent therapy resistance. Previous findings suggested that the DNA repair system is involved in the therapeutic response of cancer patients and DNA repair genes are promising targets for novel therapies. This study aimed to address complex inter-relations among gene expression levels, methylation profiles, and somatic mutations in DNA repair genes and EOC prognosis and therapy resistance status. We found significant associations of DUT expression with the presence of peritoneal metastases in EOC patients. The high-grade serous EOC subtype was enriched with TP53 mutations compared to other subtypes. Furthermore, somatic mutations in XPC and PRKDC were significantly associated with worse overall survival of EOC patients, and higher FAAP20 expression in platinum-resistant than platinum-sensitive patients was observed. We found higher methylation of RAD50 in platinum-resistant than in platinum-sensitive patients. Somatic mutations in BRCA1 and RAD9A were significantly associated with higher RBBP8 methylation in platinum-sensitive compared to platinum-resistant EOC patients. In conclusion, we discovered associations of several candidate genes from the DNA repair pathway with the prognosis and platinum resistance status of EOC patients, which deserve further validation as potential predictive biomarkers.

Modeling resistance of colorectal peritoneal metastases to immune checkpoint blockade in humanized mice

BackgroundThe immunogenic nature of metastatic colorectal cancer (CRC) with high microsatellite instability (MSI-H) underlies their responsiveness to immune checkpoint blockade (ICB). However, resistance to ICB is commonly observed, and is...

Prognostic characteristics and clinical response to immunotherapy targeting programmed cell death 1 for patients with advanced gastric cancer with liver metastases.

BackgroundThe specific efficacy of immunotherapy for patients with liver metastases of gastric cancer is unclear. This study set out to explore the treatment response and related prognostic factors for patients with liver metastases of gastric cancer treated with immunotherapy.Patients and methodsThis retrospective cohort study included 135 patients with unresectable advanced gastric cancer. According to the presence of liver metastases and/or first-line treatment with immunotherapy, patients were divided into the following three groups: I-LM(-) group(patients without liver metastases treated with immunotherapy, n=66), I-LM(+) group(patients with liver metastases treated with immunotherapy, n=36), C-LM(+) group(patients with liver metastases treated with chemotherapy and/or target therapy, n=33). Cox regression analyses were used to identify factors associated with survival in all patients and the three groups, respectively.ResultsFor the patients with liver metastases treated with immunotherapy, multivariate analysis showed that only the presence of peritoneal metastases was significantly associated with shorter PFS [hazard ratios (HR), 3.23; 95% CI, 1.12-9.32; P=0.030] and the patients with peritoneal metastases had shorter median PFS than patients without peritoneal metastases(3.1 vs 18.4 months; P=0.004), while the objective response rate was 100% in patients with HER2-positive (2 complete radiographic responses and 2 partial responses; 3 of 4 patients were still ongoing benefits [median follow-up time, 15.3 months ; interquartile range(IQR), 6.3-17.9 months]).ConclusionsThe findings suggest that patients with various types of gastric cancer liver metastases respond differently to immune checkpoint inhibitors, HER2-positive patients may derive clinical benefits from immune checkpoint inhibitors, while the presence of peritoneal metastases is associated with resistance.

P-36 Real-world outcomes in BRAFV600E metastatic colorectal cancer – the Glasgow experience

Approximately 8 - 10% of metastatic colorectal cancers (mCRC) have a BRAF V600E mutation. BRAF V600E mutant mCRC represents a distinct clinical subset with a poor prognosis. Previous treatment guidelines have been derived from subgroup analyses of non-designated BRAF V600E trials. Real world studies have shown that outcomes and treatment practices can vary widely. Here, we report on our regional practices and outcomes. We undertook a retrospective analysis of all mCRC patients with confirmed BRAF V600E mCRC diagnosed in NHS Greater Glasgow and Clyde Health Board (Scotland, UK) between 01/01/2015 - 31/12/2020. Clinical and pathological features were obtained from electronic records. Univariate analysis of prognostic factors was performed using Kaplan Meier analysis and log-rank test. Multivariate analysis was performed using Cox regression. A total of 139 patients were identified for study with 1 excluded for missing follow up information. Median age at metastatic diagnosis was 69 years, with a female preponderance (59% female, 41% male). 31% of tumours also had deficient mismatch repair (dMMR) or high levels of microsatellite instability (MSI-H). Primary tumour site was mostly right-sided (n=102, 74%), with less left-sided (n=20, 15%) and rectal (n=15, 11%) tumours. 1 patient had 2 synchronous primaries (1 right colon and 1 rectal). 64% presented with de novo metastatic disease. For those with initial loco-regional disease, the median time to metastatic progression was 10 months. The most common metastatic sites were liver (54%), peritoneal (33%), lymph node (31%), and lung (28%). 36% of patients did not receive any systemic treatment, 36% received 1 line, and 28% received 2 or more lines of treatment. Most (69%) received a cytotoxic chemotherapy doublet as first-line treatment, and 6% received triplet cytotoxic chemotherapy. 7% received immunotherapy. Among the treated patients, only 19% received some form of targeted therapy over their full treatment course, usually a combination containing an anti-EGFR inhibitor. The median overall survival was poor at 7.2 months. Features significantly associated with shorter survival were performance status (PS) of 2 or worse (p < 0.01), the presence of lymph node metastasis (p = 0.010) and peritoneal metastasis (p < 0.01), a higher modified Glasgow Prognostic Score (GPS) of 2 (p = 0.035) and a high neutrophil-lymphocyte ratio >5 (p = 0.032). Primary tumour site was also significantly associated with survival (p < 0.01), with worse survival for right-sided tumours (6.6 months), compared to 14.0 months for left-sided/rectal tumours. Using multivariate analysis, independent prognostic markers were PS, presence of lymph node metastasis, presence of peritoneal metastasis and right-sided primary tumour location. This is a representative cohort of BRAF V600E metastatic colorectal cancer patients, which confirms previously known clinical features. Of the common metastatic sites, peritoneal or lymph node metastases confer a poorer prognosis. There was not widespread adoption of more intensive triplet chemotherapy over the study time period. Overall survival is poor, and changed treatment strategies facilitated by recent clinical trial advances with targeted therapies may improve outcomes in this poor prognostic group.

P-171 Prognostic value of conversion from RAS-mutated to RAS wild-type during treatment of metastatic colorectal cancer using liquid biopsies – real-world data of two Portuguese institutions

Determination of RAS and BRAF mutational status is standard-of-care in the management of metastatic colorectal cancer (mCRC). Liquid biopsy (LB) is a powerful technology to evaluate tumor genetic heterogeneity in a noninvasive manner. Because RAS-mutations (mut) play a major role in resistance to anti-EGFR-therapy in mCRC, serial monitoring of RAS-mut with LB may be useful to guide treatment. A retrospective observational multicenter study was conducted in patients (pts) with mCRC between January/2018-December/2021. RAS and BRAF mutations were examined in the tissue biopsy at the time of metastatic diagnosis (TMD), and by LB throughout treatment (according to physician’s choice of timing), using the Idylla™ test (Biocartis). Our aim was to evaluate the prognostic impact of loss of RAS-mut status (conversion to RAS wild-type (wt) in LB) during treatment of mCRC, and to identify pts and tumor characteristics that correlate with RAS-conversion. A total of 58 LB were done in mCRC patients. Forty-one pts initially with RAS-mut tumors were studied, median (MED) age was 65 years (41-86), 26 (63%) were men. The majority had stage IV disease at diagnosis (N=25, 61%), MED 1 site of metastases (1-4), mostly hepatic (N=26, 63%) and pulmonary (N=13, 32%). Primary tumor of right-colon occurred in 18 pts (44%). Forty-pts (97,5%) underwent surgery of primary tumor, 13 (32%) complemented with metastasectomy. Curative-intent strategies were performed in 30 pts (73,2%), all receiving perioperative systemic therapy. LB was performed after a MED of 3 lines (0-7) of systemic treatment and all pts were previously treated with anti-VEGF antibodies (Abs). Conversion to RAS-wt occurred in 13 pts (32%); 8 of them (61,5%) received further treatment with anti-EGFR-Abs and 3 obtained a response (2 ongoing after 2 and 41 months). None had BRAF mutations in LB. MED follow-up after LB is 12 months, 1-year-OS is 58% (50-66) and MED OS is 15 months (11-19). A non-statistically significant numerical difference in MED OS was found between RAS-wt conversion and persistent RAS-mut pts (23 (4-40) vs 11 (5-17) months; log rank 3,8; p=0,05). Multivariate Cox regression analysis identified RAS-wt conversion as an independent prognostic factor for OS (HR 0,27; CI95 0,09-0,80; p=0,02), as well as presence of peritoneal metastases (HR 2,7; CI95 1,0-7,0; p=0,04). Moreover, more than one site of metastases at TMD was associated with RAS-conversion. This study confirms RAS-wt conversion as an independent prognostic factor for OS, with a potencial 12 months improvement in OS and a 73% relative-risk reduction of death in heavily pretreated pts with RAS-wt conversion. Although it was a retrospective study, with a small sample, these results are promising, with a rate of RAS conversion to wt superior to published data (32% versus 20% ). Several clinicopathological factors were correlated with RAS-wt conversion, which may help select pts most likely to benefit from LB during treatment. Doing LB in pts with Ras-mut tumors should be considered, preferentially early in the disease-course, since loss of mutation represents an opportunity for treatment with anti-EGFR-therapy otherwise unlikely.

Implications of peritoneal cancer index distribution on patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

ObjectivesPeritoneal cancer index (PCI) score is a common prognostication tool in peritoneal metastases (PM). We hypothesize that the distribution of PCI score and involvement of specific regions affects survival and morbidity outcomes.MethodsData was collected from a prospective database of patients who underwent CRS and HIPEC for PM at the National Cancer Centre Singapore. We evaluate the relationship between PCI, PCI distribution, and survival and morbidity outcomes.ResultsOne hundred and fifty-two patients underwent CRS and HIPEC with a median PCI score of nine (range 0–31). Median overall survival (OS) and progression free survival (PFS) were 43 and 17 months, respectively. Region six (pelvis) was most commonly involved and had the highest frequency of heavy disease burden. Presence of PM in the lower abdomen, flanks, and small bowel were associated with poorer OS (p=0.01, 0.03, <0.001) and PFS (p=0.04, 0.02, <0.001). Involvement of porta hepatitis predicted poorer OS but not PFS (p=0.03). Involvement of the gastric antrum resulted in higher rates of postoperative complications.ConclusionsThe pattern of PCI distribution may be associated with varying survival and morbidity outcomes.