Normal CA-125 Research Articles

Neoadjuvant therapy impact in early pancreatic cancer: "bioborderline" vs. "non-bioborderline".

To analyze the results of the neoadjuvant treatment of patients in our center with early pancreatic cancer. Eighty-four patients with early pancreatic cancer (I-II) were included, of which 59 were considered "bioborderline" (carbohydrate antigen [CA] 19-9 > 37 U/L), and 25 were considered "non-bioborderline" (CA19-9 < 37 U/L). The R0 resection rate, presence of negative nodes, survival, and recurrence rates were analyzed in two groups, the NEO group (neoadjuvant + surgery) and the non-NEO group (upfront surgery). A 28.6% pathologic complete response was observed in the NEO group of the whole sample. The residual R0 was 85.7%, and nodes were negative in 78.6% of the patients in the NEO group of bioborderline patients. All non-bioborderline patients treated with neoadjuvant were R0, and no affected nodes were observed in any of them. The median overall survival (OS) in patients with elevated CA19-9 levels in the NEO group was 31.4 months vs. 13.1 months in the non-NEO (log-rank test p = 0.006), with a 62% relative reduction in the mortality rate (hazard ratio = 0.38, 95% confidence interval: 0.20-0.79; p = 0.008). The median OS in patients with normal CA19-9 levels in the NEO group was 65.9 months vs. 16.2 months in the non-NEO group, without statistically significant differences between the two but with a trend toward significance (log-rank test p = 0.08). A neoadjuvant strategy seemed to improve local control and the survival of patients with early pancreatic cancer, both those with elevated CA19-9 and normal marker levels.

Tailoring Adjuvant Chemotherapy to Biologic Response Following Neoadjuvant Chemotherapy Impacts Overall Survival in Pancreatic Cancer

BackgroundThe role of postoperative chemotherapy in patients with resected pancreatic cancer who receive neoadjuvant treatment is unknown. Clinicians use changes in CA19-9 and histopathologic scores to assess treatment response. We sought to investigate if CA19-9 normalization in response to NAT can help guide the need for postoperative treatment. MethodsPatients with elevated baseline CA19-9 (CA19-9 > 37U/mL) who received NAT followed by surgery between 2011 and 2019 were retrospectively reviewed. Treatment response was determined by CA19-9 normalization following NAT and histopathologic scoring. The role of postoperative chemotherapy was analyzed in light of CA19-9 normalization and histopathologic response. ResultsWe identified and included 345 patients. Following NAT, CA19-9 normalization was observed in 125 patients (36.2%). CA19-9 normalization was associated with a favorable histopathologic response (41.6% vs 23.2%, p < 0.001) and a lower ypT (p < 0.001) and ypN stage (p = 0.003). Receipt of adjuvant chemotherapy was associated with improved overall survival in patients in whom CA19-9 did not normalize following NAT (26.8 vs 16.4 months, p = 0.008). In patients who received 5FU-based NAT and in whom CA19-9 did not normalize, receipt of 5FU-based adjuvant chemotherapy was associated with improved OS (p = 0.014). ConclusionCA19-9 normalization in response to NAT was associated with favorable outcomes and can serve as a biomarker for treatment response. In patients where CA19-9 did not normalize, receipt of postoperative chemotherapy was associated with improved OS. These patients also benefited from additional 5FU-based postoperative chemotherapy following 5FU-based NAT.

S2007 Chronic Lymphocytic Leukemia Presenting as Colonic Ulcers

Introduction: Chronic Lymphocytic Leukemia (CLL) accounts for 25% of leukemias. One can present with hepatomegaly, splenomegaly, and lymphadenopathy. CLL infiltration in the gastrointestinal (GI) mucosa is rare. Colonic CLL can develop late in the disease course with mild to no GI symptoms. Awareness of CLL and its various extra-nodal presentations allow for prompt diagnosis and treatment. Case Description/Methods: An 80-year-old female with untreated CLL presented with 2 months of rectal bleeding. She denied weight loss, anorexia, night sweats, blood thinners, and NSAID use. She had WBC 34.3, platelets 139, and a normal Hgb of 13.2. Colonoscopy showed ulcerations at the ileocecal valve and transverse colon, a 30 mm ascending colon polyp, and multiple 10-20 mm transverse and descending colon polyps. Pathology showed only chronic inflammation of the ulcerated regions, and a sessile serrated adenoma at the ascending colon. The remaining polyps were not removed due to concern for cancer and potential colectomy. A CT chest, abdomen, and pelvis was unremarkable. Tumor markers showed CEA 8 and normal Ca19-9 and Ca-125. Due to an unclear diagnosis, a second colonoscopy was performed with repeat biopsies and removal of all polyps in the descending and sigmoid colon. Pathology results were negative for inflammatory bowel disease and infection. The polyps were tubular adenomas and hyperplastic. However, immunohistochemical analysis was positive for CD5/CD43 and CD23, indicative of CLL in the ulcerated mucosa. Treatment options were discussed with surgery and oncology. The patient was offered right colon resection or endoscopic removal of the remaining polyps prior to chemotherapy (Figure). Discussion: Colorectal lymphomas are rare and account for 1% of all GI malignancies with CLL usually found proximal to the hepatic flexure. In this case, the presence of ulcerations and large polyps were concerning for colorectal cancer. However, the initial work-up was negative. After a repeat colonoscopy, testing for specific CLL markers was requested. In a review of literature, chemotherapy alone for colonic CLL had a perforation risk of 15%. While it is unclear if surgical treatment is beneficial, it is a potential option. Due to the high risk of perforation on chemotherapy, recommendations included right hemicolectomy or endoscopic removal of the remaining polyps prior to starting treatment. This demonstrates the importance of knowing the varying presentations of colonic CLL as its treatment may require multidisciplinary discussion.Figure 1.: Colonic ulcers located at the transverse colon (top left) and IC valve (top right). H&E stain of the colonic mucosa (bottom) that showed positive markers for CLL on IHC analysis.

Preoperative serum CA19-9 should be routinely measured in the colorectal patients with preoperative normal serum CEA: a multicenter retrospective cohort study

ObjectiveWhether preoperative serum carbohydrate antigen 19–9 (CA19-9) is an independent prognostic factor and there are interactions of serum CA19-9 with carcinoembryonic antigen (CEA) on the risk of recurrence in colorectal cancer (CRC) patients are still not clarified.MethodsConsecutive patients with CRC who underwent curative resection for stage II-III colorectal adenocarcinoma at five hospitals were collected. Based on Cox models, associations of preoperative CA19-9 with recurrence-free survival (RFS) and overall survival (OS) were evaluated in patients with or without elevated CEA, and interactions between CEA and CA19-9 were also calculated. Restricted cubic spline (RCS) curves were used to evaluate the associations between preoperative CA19-9 and CRC outcomes on a continuous scale.ResultsA total of 5048 patients (3029 [60.0%] men; median [interquartile range, IQR] age, 61.0 [51.0, 68.0] years; median [IQR] follow-up duration 46.8 [36.5–62.4] months) were included. The risk of recurrence increased with the elevated level of preoperative CA19-9, with the slope steeper in patients with normal CEA than those with elevated CEA. Worse RFS was observed for elevated preoperative CA19-9 (> 37 U/mL) (n = 738) versus normal preoperative CA19-9 (≤ 37 U/mL) (n = 4310) (3-year RFS rate: 59.4% versus 78.0%; unadjusted hazard ratio [HR]: 2.02; 95% confidence interval [CI]:1.79 to 2.28), and significant interaction was found between CA19-9 and CEA (P for interaction = 0.001). Increased risk and interaction with CEA were also observed for OS. In the Cox multivariable analysis, elevated CA19-9 was associated with shorter RFS and OS regardless of preoperative CEA level, even after adjustment for other prognostic factors (HR: 2.08, 95% CI:1.75 to 2.47; HR: 2.25, 95% CI:1.80 to 2.81). Subgroup analyses and sensitivity analyses yielded largely similar results. These associations were maintained in patients with stage II disease (n = 2724).ConclusionsPreoperative CA19-9 is an independent prognostic factor in CRC patients. Preoperative CA19-9 can be clinically used as a routine biomarker for CRC patients, especially with preoperative normal serum CEA.

Prognostic factors in conversion surgery following nab-paclitaxel with gemcitabine and subsequent chemoradiotherapy for unresectable locally advanced pancreatic cancer: Results of a dual-center study.

In pancreatic ductal adenocarcinoma (PDAC), only radical surgery improves long-term survival. We focused on surgical outcome after induction gemcitabine along with nab-paclitaxel (GnP) and subsequent chemoradiotherapy (CRT) with S-1 administration for unresectable locally advanced (UR-LA) PDAC. We retrospectively analyzed 144 patients with UR-LA PDAC between 2014 and 2020. The first-line regimen of induction chemotherapy was GnP for 125 of the 144 patients. Of the 125 patients who received GnP, 41 who underwent radical resection after additional preoperative CRT were enrolled. We evaluated the prognostic factors for this treatment strategy. The median length of preoperative GnP was 8.8months, and 30 (73%) patients had normalized CA19-9 levels. R0 resection was achieved in 36 (88%) patients. Postoperative major complications of ≥Clavien-Dindo grade IIIa developed in 16 (39%) patients. With a median follow-up of 35.2months, 14 (34%) patients developed distant metastasis postoperatively. Using the Kaplan-Meier method, prognostic analysis of the 41 cases revealed the 3-y overall survival rate (OS) was 77.4% and the 5-y OS was 58.6%. In univariate analysis, length of preoperative GnP (≥8months), CA19-9 normalization, and good nutritional status at operation (prognostic nutritional index ≥41.7) were significantly associated with favorable prognosis. Multivariate analysis revealed CA19-9 normalization (hazard ratio [HR] 0.23; P=.032) and prognostic nutritional index ≥41.7 (HR 0.05; P=.021) were independent prognostic factors. For surgical outcome after induction GnP and subsequent CRT for UR-LA PDAC, CA19-9 normalization and maintenance of good nutritional status during treatment until surgery were important for prolonged prognosis.

Baseline self-perceived risks and risk-reducing behaviors in Lynch syndrome patients undergoing annual surveillance versus risk-reducing surgery (449)

<b>Objectives:</b> There is a paucity of data regarding self-perceived risks of cancer and attitudes toward potential risk-reducing strategies in patients diagnosed with Lynch Syndrome (LS). The objective of the study was to describe self-perceived risk and knowledge of riskreducing behaviors in LS patients and determine differences in those undergoing risk-reducing surgery (RRS) versus annual surveillance. <b>Methods:</b> This prospective cohort study enrolled patients diagnosed with LS based on pathogenic variants in mismatch repair genes but unaffected by gynecologic cancer from February 2015 to January 2021. Participants completed questionnaires evaluating attitudes and behaviors related to cancer screening and self-perceived cancer risk. Patients in both RRS and surveillance completed these questionnaires at baseline, three months, and one year. We hereby report responses to the questionnaires at baseline. Statistical analysis was done by reporting proportions and Chi-square for significance. <b>Results:</b> During the study period, 81 patients were enrolled; 41 elected to undergo RRS, and 40 underwent annual surveillance. Patients in the RRS group were significantly older (46 vs 32 years, p<0.001). The most common LS-associated mutation was <i>MSH6</i> (34.6%). There was no significant difference in risk perception between groups. Most patients (94.7%) perceived themselves to be at "somewhat to much higher" risk of endometrial cancer than women their age, and most (44.7%) cited this risk between 33-61%. Most (93.4%) perceive their risk of ovarian cancer to be "somewhat to much higher" than the general population; a majority (36%) rated their risk of ovarian cancer to be between 13-61%. Patients in the surveillance group were more likely to be aware of risk-reducing steps (89.7% vs 58.6, p=0.007), and 42.9% rated these strategies as very or extremely effective. The most common risk-reducing behavior was mindfulness of abnormal symptoms, such as bleeding (97.1%). Prior to enrollment, a significant proportion reported engagement in cancer surveillance (51.4% ultrasound and 39% endometrial biopsy). The most common symptom worrisome to pre-menopausal patients was vaginal bleeding with clots (37.3%), and the majority (85%) would seek help either immediately or in case of no resolution within four weeks. Over half of patients (51.7%) were very or extremely concerned about abdominal pain, and 76.7% were likely to seek help if the pain didn't resolve immediately or within four weeks. The majority of patients were "somewhat to completely reassured" with a normal CA-125 (72.4%), transvaginal ultrasound (74.9%), and endometrial biopsy (72.4%). <b>Conclusions:</b> Patients with LS appropriately considered their risk of endometrial/ovarian cancer higher than the general population and were likely to engage in perceived risk-reducing behaviors, even prior to their enrollment into the program. Normal surveillance tests may create false reassurance and may be addressed by increased counseling regarding limitations of gynecologic cancer screening in LS.

Abstract 3390: Preliminary results for a novel single extracellular vesicle assay for early stage ovarian cancer: The power of co-localized detection of surface biomarkers

Abstract Introduction: Ovarian cancer (OC) is one of the deadliest cancers, with 314,000 new cases and 207,000 deaths globally in 2020. Serum CA125 has been explored as an OC biomarker for the past 40 years, but lacks sensitivity for early stage OC and is not recommended for screening average-risk, asymptomatic women. We hypothesize that co-localization of biomarkers on the surface of individual extracellular vesicles (EVs), which are shed into the circulation by cancer cells, may lead to development of a blood test for early stage OC. We evaluated the potential of our approach in detecting early stage OC in clinical samples. Methods: We isolated EVs using size-exclusion chromatography and immunoaffinity capture, and detected biomarkers co-localized on the surface of individual EVs with proximity ligation qPCR. Using this approach, we evaluated 49 antibody combinations recognizing 2 or more biomarkers. Each combination consisted of 1 capture antibody and 2 oligonucleotide-tagged detection antibodies. We tested plasma samples from women with early stage I/II high-grade serous ovarian carcinoma (HGSOC)(n=18; 48-80 yr, med 57) and late stage HGSOC (n=24; 37-80 yr, med 54). HGSOC samples were sourced from 2 commercial vendors. Controls comprised samples from women with benign ovarian masses (n=26; 23-76 yr, med 39.5) sourced from a single vendor, and samples prospectively collected by Mercy from healthy women with no cancer history (n=24; 22-72 yr, med 52.5). PCR cycle threshold (Ct) values were measured for each of 49 combinations and data was evaluated using univariate analysis. Performance was compared to plasma CA125 measured at Mercy by commercial ELISA. Results: 8 of 49 combinations distinguished all stages of HGSOC relative to benign and healthy controls with AUCs ranging from 0.86 (95% CI 0.78-0.94) to 0.95 (95% CI 0.90-1.00), comparable to CA125 with an AUC of 0.87 (95% CI 0.79-0.95). One of the most effective combinations (STn, BST2, MUC1) had a sensitivity of 0.78 (95% CI 0.52-0.94) at a specificity of 0.96 (95% CI 0.87-0.99) in detecting early stage HGSOC. This combination also detected HGSOC in 6 of 11 women (3 early stage, 3 late stage) with normal CA125 (&amp;lt; 25 U/mL) and correctly classified 7 of 8 women with benign masses and high CA125 (&amp;gt; 25 U/mL). Conclusions: These preliminary data suggest that co-localization of surface biomarkers in single EVs may provide an effective means to identify women with early stage HGSOC, including those with normal CA125, while avoiding false positives in women with benign masses and high CA125. Despite the inherent challenges associated with commercial samples, our finding that several combinations detected early stage HGSOC is promising. Statistically powered studies with curated repository specimens are underway to refine combinations and independently validate our assay for early stage OC detection. Citation Format: Laura T. Bortolin, Daniel P. Salem, Sanchari Banerjee, Kelly M. Biette, Delaney M. Byrne, Anthony D. Couvillon, Peter A. Duff, Jonian Grosha, MacKenzie Sadie King, Christopher R. Sedlak, Ibukunoluwapo O. Zabroski, Claire Alexander, Karen Copeland, Daniel Gusenleitner, Emily S. Winn-Deen, Eric K. Huang, Bo R. Rueda, Joseph Charles Sedlak. Preliminary results for a novel single extracellular vesicle assay for early stage ovarian cancer: The power of co-localized detection of surface biomarkers [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 3390.

The Modified Glasgow Prognostic Score Predicts Survival in Gastric Cancer Patients with Normal CEA and CA19-9

Background Traditionally, serum CEA and CA19-9 levels are good prognostic factors for gastric cancer. Many gastric cancer patients do not have elevated CEA or CA19-9 levels even at a very advanced stage. This study investigates the significance of the modified Glasgow prognostic score (mGPS) for the survival of gastric cancer patients with normal CEA and CA19-9. Methods We retrospectively examined 488 curatively resected gastric cancer patients with normal preoperative serum levels of CEA and CA19-9 to evaluate the prognostic ability of mGPS for overall survival. The prognostic significance was analyzed by univariate and multivariate analyses. Results Age, hemoglobin, white cell count, and neutrophils were each significantly correlated with the mGPS. Multivariate analyses showed that tumor location (HR, 0.803; 95% CI, 0.667–0.966; P=0.020), TNM stage (HR, 2.714; 95% CI, 2.250–3.275; P < 0.001), and mGPS (HR, 1.042; 95% CI, 1.105–1.772; P=0.023) were significantly associated with overall survival. Significant correlations were found between overall survival and mGPS. The Kaplan–Meier analysis demonstrated significant differences among patients with mGPS of 0, 1, and 2 (P < 0.001), with the mortality rate being higher for patients with a higher mGPS. Conclusion The mGPS can predict survival in gastric cancer patients with normal CEA and CA19-9.

GRECO-2: A randomized, phase 2 study of stereotactic body radiation therapy (SBRT) in combination with rucosopasem (GC4711) in the treatment of locally advanced or borderline resectable nonmetastatic pancreatic cancer.

TPS4184 Background: While treatment of pancreatic cancer has advanced, survival rates remain low. Stereotactic body radiotherapy (SBRT; high dose per fraction radiation) may exhibit improved clinical outcomes in locally advanced pancreatic cancer but carries potential gastrointestinal toxicity risks (Zhong 2017). Rucosopasem (GC4711) is one of a class of investigational selective dismutase mimetics that rapidly and specifically converts superoxide to hydrogen peroxide (Riley 2006). Studies have shown that normal cells tolerate hydrogen peroxide fluxes better than cancer cells (Doskey 2016). As radiation response modifiers, dismutase mimetics have the potential to increase tumor control of SBRT without compromising radiation safety (El-Mahdy 2020, Sishc 2021). In a pilot phase 1/2 trial in patients with pancreatic cancer, avasopasem, a dismutase mimetic related to rucosopasem, nearly doubled median overall survival in patients receiving SBRT vs placebo plus SBRT. Improvements versus placebo were also observed in local tumor control, time to metastases, and progression-free survival. Altogether, these data support the hypothesis that rucosopasem may improve survival and the benefit-risk ratio of SBRT by improving efficacy without increasing gastrointestinal toxicity. Materials/Methods: GRECO-2 is a phase 2, multicenter, randomized, double-blind, placebo-controlled study (NCT04698915) to determine the effect of adding rucosopasem to SBRT on overall survival in patients with borderline resectable or locally advanced, unresectable nonmetastatic pancreatic cancer following initial chemotherapy with a FOLFIRINOX-based regimen or a gemcitabine doublet. Approximately 160 patients will be randomized (approximately 35 sites) to receive rucosopasem 100 mg or placebo via IV infusion over 15 minutes, prior to each SBRT fraction (5 x 10 Gy). Patients judged to be resectable will undergo surgical exploration within 8 weeks after SBRT. The primary endpoint is overall survival. Secondary endpoints include progression-free survival, locoregional control, time to metastasis, surgical resection rate, RO resection rate, best overall response, in-field local response, and safety (acute and late toxicities). Exploratory endpoints include PRO-CTCAE and CA19-9 normalization. This trial is now enrolling. Clinical trial information: NCT04698915.

Prognostic Impact of Pathology, Cytoreduction, and Tumor Markers in Pseudomyxoma Peritonei.

The pathologic classification of pseudomyxoma peritonei is controversial. This study aimed to standardize the histopathological evaluation of pseudomyxoma peritonei and identify the clinicopathological factors associated with survival. A pathologic review was performed to systematize the pathology report and verify the relationship between clinical features and survival. Terminology was based on the World Health Organization and Peritoneal Surface Oncology Group International definitions. Preoperative serum levels of carcinoembryonic antigen, CA19-9, and CA-125 were evaluated to determine their association with overall survival (OS) and ability to predict CC0-1 cytoreduction. Among 109 patients with carcinomas resulting from primary appendiceal neoplasms, 72 had pseudomyxoma peritonei of appendiceal origin and underwent debulking surgery. CC0-1 cytoreduction and CC2-3 cytoreduction were achieved in 61% and 39% of patients, respectively. Patients in the CC0-1 and CC2-3 groups had an OS of 122.80 and 32.92mo, respectively. The histologic grade was associated with CC0-1 cytoreduction; however, it did not influence OS. Patients with CC0-1 cytoreduction, acellular mucin, and low-grade lesions had better disease-free survival. Higher preoperative CA19-9 levels were associated with poor OS. Normal carcinoembryonic antigen values were associated with 100% sensitivity for predicting CC0-1. CA19-9 levels of 625 U/mL were associated with a low possibility of predicting CC0-1. Histologic grades are associated with disease-free survival when CC0-1 cytoreduction is achieved. Normal preoperative CA19-9 levels were associated with a better OS. CC0-1 cytoreduction is the main determinant of longer survival.

Biomarker-Based Models for Preoperative Assessment of Adnexal Mass: A Multicenter Validation Study.

Simple SummaryOvarian cancer (OC) is the deadliest genital tumor in women. In this multicenter study, we developed three new diagnostic models based on serum proteins and patient age. All models were then validated using data from centers other than those used for the model development. We also compared the performance of these models with common singular markers (CA125, HE4) and algorithms (ROMA-50 and the Copenhagen Index). We used modern technology (Luminex®, Austin, TX, USA) that enables the simultaneous determination of several biomarkers in a small amount of blood. A combination of patient age with four to six markers performed best: CA125, osteopontin, prolactin, macrophage migration inhibitory factor, and, eventually, HE4 and leptin. Our models were better than the ROMA-50 index but did not outperform the Copenhagen Index. In postmenopausal patients, all the newly developed models performed excellently. Unfortunately, none of the models tested improved the diagnosis in premenopausal patients and those missed due to normal CA125 levels.Ovarian cancer (OC) is the most lethal genital malignancy in women. We aimed to develop and validate new proteomic-based models for non-invasive diagnosis of OC. We also compared them to the modified Risk of Ovarian Malignancy Algorithm (ROMA-50), the Copenhagen Index (CPH-I) and our earlier Proteomic Model 2017. Biomarkers were assessed using bead-based multiplex technology (Luminex®) in 356 women (250 with malignant and 106 with benign ovarian tumors) from five European centers. The training cohort included 279 women from three centers, and the validation cohort 77 women from two other centers. Of six previously studied serum proteins (CA125, HE4, osteopontin [OPN], prolactin, leptin, and macrophage migration inhibitory factor [MIF]), four contributed significantly to the Proteomic Model 2021 (CA125, OPN, prolactin, MIF), while leptin and HE4 were omitted by the algorithm. The Proteomic Model 2021 revealed a c-index of 0.98 (95% CI 0.96, 0.99) in the training cohort; however, in the validation cohort it only achieved a c-index of 0.82 (95% CI 0.72, 0.91). Adding patient age to the Proteomic Model 2021 constituted the Combined Model 2021, with a c-index of 0.99 (95% CI 0.97, 1) in the training cohort and a c-index of 0.86 (95% CI 0.78, 0.95) in the validation cohort. The Full Combined Model 2021 (all six proteins with age) yielded a c-index of 0.98 (95% CI 0.97, 0.99) in the training cohort and a c-index of 0.89 (95% CI 0.81, 0.97) in the validation cohort. The validation of our previous Proteomic Model 2017, as well as the ROMA-50 and CPH-I revealed a c-index of 0.9 (95% CI 0.82, 0.97), 0.54 (95% CI 0.38, 0.69) and 0.92 (95% CI 0.85, 0.98), respectively. In postmenopausal women, the three newly developed models all achieved a specificity of 1.00, a positive predictive value (PPV) of 1.00, and a sensitivity of >0.9. Performance in women under 50 years of age (c-index below 0.6) or with normal CA125 (c-index close to 0.5) was poor. CA125 and OPN had the best discriminating power as single markers. In summary, the CPH-I, the two combined 2021 Models, and the Proteomic Model 2017 showed satisfactory diagnostic accuracies, with no clear superiority of either model. Notably, although combining values of only four proteins with age, the Combined Model 2021 performed comparably to the Full Combined Model 2021. The models confirmed their exceptional diagnostic performance in women aged ≥50. All models outperformed the ROMA-50.

Laparoscopic Left Hemihepatectomy for Intrahepatic Cholangiocellular Carcinoma: An Adequate Lymphadenectomy is Also Possible in Artery Variation

BackgroundLaparoscopic liver resection (LLR) is becoming essential in the treatment of malignant liver tumors but only a few reports exist about LLR for intrahepatic cholangiocarcinoma (IHCC).MethodsWe present a video of a laparoscopic left hemihepatectomy with lymphadenectomy for IHCC.Case presentationA 67-year-old asymptomatic male underwent a routine abdominal ultrasound, revealing a 15 × 9 mm solid nodular iso-hyperechoic lesion, located in SIII, with SII/III biliary duct dilation. Magnetic resonance imaging confirmed a 32 × 22 mm lesion in SII/III, with mild hyper-intensity on T2-weighted images and strong hypo-intensity on T1-weighted images. After administration of contrast medium, the lesion showed light peripheral enhancement on the portal and delayed phases, and hypo-intensity on the hepatospecific phase. No relevant comorbidities were reported (KPS 100). Laboratory tests showed normal liver function and normal CA19-9 levels. A laparoscopic left hemihepatectomy was indicated.ResultsOperative time was 330 min. Four intermittent Pringle maneuver cycles were applied and no blood transfusions were administered. Intraoperative ultrasound confirmed preoperative findings and additionally highlighted involvement of the SIV duct. A full replacing right hepatic artery arising from the superior mesenteric artery was identified and was preserved during hilar dissection. Postoperative course was uneventful and the patient was discharged on postoperative day 3. The pathology report indicated cholangiocellular carcinoma pT1bN0. Twelve lymph nodes were retrieved.ConclusionsAccording to recent literature reports and our experience, laparoscopic surgery for intrahepatic cholangiocellular carcinoma should be considered feasible and safe in selected patients. Hepatic artery variations allow for adequate lymphadenectomy. Oncological long-term results require multicenter randomized studies in order to be validated.

Elevated levels of CA125 (MUC16) in metastatic gastric cancer as a strong predictor of poor survival

Introduction: CA125 is an extracellular domain of MUC16 glycoprotein. The clinical significance of serum CA125 has been most extensively studied in ovarian cancer. The significance of serum CA125 in gastric cancer has not been fully elucidated. There is evidence that MUC16 overexpression is associated with poor survival in patients with metastatic gastric cancer. We have not found any research papers on the correlation between the levels of serum CA125 and MUC16 overexpression.Objective: The objective of the study was to assess the effects of elevated CA125 levels in patients with metastatic cancer on the long‑term results (time to disease progression and overall survival).Materials and methods: CA125 was determined in the serum before the start of first‑line chemotherapy in 75 patients (45 males and 30 females) with metastatic gastric cancer. The mean age of the patients was 61,3 (26,7–84,9) years. Synchronous metastases were observed in 85 % of patients: 57,3 % in the peritoneum, 37,3 % in the liver, 5,4 % at other sites. Palliative gastrectomy and metastasectomy were performed in 28 % and 20 % of patients, respectively. Monotherapy, doublet and triplet chemotherapy regimens were used in 6,7 %, 58,7 % and 36,0 % of patients, respectively.Results: the analysis showed that elevated levels of CA125 (&gt; 37 IU/mL) were associated with a significant reduction in median time to progression (3,5 months (CI 2,87–9,53) vs 6,2 months, р = 0.001 (CI 2,02–4,9)) and overall survival (5,1 months (CI 6,07–28,1) vs 17,1 months (CI 3,5–6,67), р = 0.001). One‑factor ANOVA showed that factors with the strongest effects on the survival rates included the location of metastases (peritoneum), tumor histology (adenocarcinoma/signet ring cell carcinoma), the use of palliative gastrectomy and metastasis resection. A multi‑factor ANOVA showed that the only favorable prognostic factors in terms of overall survival rates were normal CA125 levels (HR 0,39 (95 % CI 0,18–0,84), р = 0.001) and the use of palliative gastrectomy (HR 0,23 (95 % CI 0,1–0,58), р = 0.001). The use of triplet chemotherapy regimens allowed to slightly improve the overall survival rates in the group of patients with elevated CA125 levels; however, the differences were not statistically significant (6,7 months vs 4Ю0 months, p = 0.29).Conclusion: Elevated levels of CA125, which reflect MUC16 overexpression to a certain extent, is a strong independent predictor of poor outcome in metastatic gastric cancer. Currently, a possible way to overcome this negative impact is to use more intensive chemotherapy regimens. However, further research should be aimed at finding adequate targets and ways of neutralizing the negative impact of MUC16 overexpression in patients with metastatic gastric cancer.

Nomogram to predict feasibility of minimally invasive interval debulking surgery in advanced ovarian cancer

ObjectiveCurrently, there is no clear guidance defining the ideal candidate for minimally invasive interval debulking surgery. This study aimed to identify predictive factors for a minimally invasive approach in patients...

DO HIGH PRE-OPERATIVE CA-125 LEVELS PREDICT EARLY RECURRENCE IN PATIENTS WITH HIGH-GRADE EPITHELIAL OVARIAN CANCER ?

Ponte Academic JournalAug 2022, Volume 78, Issue 8 DO HIGH PRE-OPERATIVE CA-125 LEVELS PREDICT EARLY RECURRENCE IN PATIENTS WITH HIGH-GRADE EPITHELIAL OVARIAN CANCER ?Author(s): Nilufer Bulut ,Tanju KapaganJ. Ponte - Aug 2022 - Volume 78 - Issue 8 doi: 10.21506/j.ponte.2022.8.8 Abstract:Background CA-125 is used as a marker in the diagnosis, treatment, and follow-up of ovarian cancers. High CA-125 levels indicate a high tumor burden, large ascites volume, and advanced stage. In the present study, the predictive value of CA-125 for the prognosis of ovarian cancer patients was determined. Materials-Methods The data of 173 patients diagnosed with ovarian cancer between 2009 and 2021 were analyzed retrospectively. CA-125 values before primary treatment were recorded. All patients underwent neoadjuvant chemotherapy or primary tumor surgery. Patients with normal CA-125 values at the end of treatment, and those with residual tumor, were followed up until the first recurrence. Disease-free and overall survival were analyzed. Results According to the preoperative CA-125 values, the disease-free survival time before treatment in patients with CA-125 levels of 0–40, 41–120, and &gt; 121 U/ml was 73, 59.8, and 54 months, respectively; the differences were not statistically significant (p = 0.174). Patients with a ≥ 3-fold increase in their CA-125 value at recurrence had shorter overall survival (0–40 U/ml: 86 months; 41–120 U/ml: 60 months; &gt; 121 U/ml: 54 months; p = 0.025). For patients without residual tumor after surgery, overall survival was 61 months, but it was significantly shorter (38 months) in those with residual tumor &gt; 1 cm (p=0.001). Conclusion Levels of the tumor marker CA-125 are used to determine the response to treatment, residual tumor, and disease recurrence in ovarian cancer patients. Although elevated CA-125 levels alone do not contribute to the prognosis, patients with values 3-fold higher than before treatment had shorter overall survival. Download full text:Check if you have access through your login credentials or your institution Username Password

CA125 normalization within 60 days as an independent prognostic factor for patients with advanced epithelial ovarian cancer.

CA125 level normalization at different chemotherapy cycles has been reported to be a prognosticator in advanced epithelial ovarian cancer. In the present study, we investigated whether the time (in days) to CA125 normalization or nadir during treatment could be used as markers to predict survival. Patients with FIGO stage III-IV epithelial ovarian cancer treated with cytoreductive surgery followed by adjuvant chemotherapy between 2008 and 2016 were enrolled in this retrospective study. Clinicopathological characteristics, changes in CA125 level during treatment, and survival outcomes were analyzed. Time-dependent receiver operating characteristic curve analysis was used to determine the optimal cut-off values of the time to normalization and time to nadir of CA125 levels to predict survival. Univariate and multivariate Cox regression analysis were used to examine the impact of each variable on survival. A total of 106 patients were included in the analysis. The optimal cut-off values for the time to normalization and nadir for predicting survival were 60 and 194 days, respectively. In Kaplan-Meier survival analysis, CA125 level normalization ⩽ 60 days and CA125 ⩽ 35 u/mL after the third cycle, and CA125 level ⩽ 10 u/mL after the sixth cycle of chemotherapy were associated with significantly better 5-year progression-free survival (PFS) and overall survival (OS). In multivariate analysis, only CA125 level normalization > 60 days was significantly associated with poor survival outcomes (PFS, HR 2.62 [95% CI: 1.54, 4.45], p= 0.004; OS, HR 2.40 [95% CI: 1.19, 4.81], p= 0.014). Normalization of CA125 level within 60 days after cytoreductive surgery followed by adjuvant chemotherapy in patients with advanced ovarian epithelial cancer could be used as a marker to predict survival.

Combination ATR and PARP Inhibitor (CAPRI): A phase 2 study of ceralasertib plus olaparib in patients with recurrent, platinum-resistant epithelial ovarian cancer

ObjectivePlatinum-resistant, high-grade serous ovarian cancer (HGSOC) has limited treatment options. Preclinical data suggest that poly(ADP-ribose) polymerase inhibitors (PARPi) and ataxia telangiectasia and Rad3-related kinase inhibitors (ATRi) are synergistic. CAPRI (NCT03462342) is an investigator-initiated study of olaparib plus ceralasertib in recurrent HGSOC. Herein, we present results from the platinum-resistant cohort. MethodsA Simon 2-stage design was utilized. Platinum-resistant HGSOC patients received ceralasertib 160 mg orally daily, days 1–7 and olaparib 300 mg orally twice daily, days 1–28 of a 28-day cycle until toxicity or progression. Primary endpoints were toxicity and efficacy including objective response rate (ORR) by RECIST. Secondary endpoint was progression-free survival (PFS). The null hypothesis (≤5% ORR) would be rejected if there were ≥ 1 responses in 12 patients. ResultsFourteen PARPi-naïve patients were evaluable for toxicity; 12 were evaluable for response. Three had BRCA1 mutations (1 germline, 2 somatic). Adverse events possibly related to treatment were primarily grade (G) 1/2. G3 toxicities included nausea (14.3%), fatigue (7.1%), anorexia (7.1%), and anemia (7.1%). No objective responses occurred. Best response was stable disease in 9 patients and progressive disease in three. Five patients had a ≥ 20% to <30% reduction in disease burden, including 3 with BRCA1 mutations. Three of 11 patients (27%; 2 with BRCA1 mutations) evaluable by Gynecologic Cancer Intergroup criteria had >50% CA-125 decline, including 2 with CA-125 normalization. Median PFS was 4.2 months overall (90% CI:3.5–8.2) and 8.2 months (3.6 months–not determined) for patients with BRCA1 mutations. ConclusionsOlaparib plus ceralasertib is well-tolerated. No objective responses occurred, though a signal of activity was seen particularly in disease associated with BRCA1. Further evaluation of this combination should include alternate dosing strategies in genomically-selected populations.

CA-125 and other prognostic factors associated with survival in stage I epithelial ovarian cancer: a study of 15,882 patients

<h3>Objectives:</h3> To investigate the prognostic value of demographic and clinicopathologic factors including CA-125 levels in patients with stage I epithelial ovarian carcinoma. <h3>Methods:</h3> Data was obtained from the National Cancer Database (NCDB PUF 2016). Patients were diagnosed with stage I epithelial ovarian cancer between 2004 and 2015. CA-125 results were reported as abnormal if they were ≥35 units/mL before treatment. Kaplan-Meier method, log-rank test, and multivariate Cox proportional hazards modeling were used for statistical analyses. <h3>Results:</h3> Of 15,882 patients with stage I epithelial ovarian carcinoma, the median age was 55 (range 18-90). The majority of patients were White (80.4%) and the remainder were Hispanic (6.4%), Black (6.1%), and Asian (5%). Stage IA, IB, IC, and stage I NOS were found in 54.2%, 3.8%, 36.3%, 5.7% of patients, respectively. There were 25.2% with endometrioid carcinoma, 20.9% with serous carcinoma, 20.7% with mucinous carcinoma, 15.6% with clear cell carcinoma and 17.6% with other epithelial subtypes. The 5-year overall survival (OS) was 86.0%. Black race was associated with worse OS at 82.6% compared to 85.6% of Whites (P=0.024). Those with higher substage IC vs IA and IB had worse survivals (82.7% vs 88.4% and 85.3%; P<0.001 and P=0.042). Those with clear cell or serous carcinoma had poorer outcomes compared to those with mucinous (83.0% or 84.4% vs 87.2%; P<0.001 or P=0.016) and endometrioid carcinoma (90.9%; P<0.001 or P<0.001). Tumors with LVSI had associated survival of 75.2% compared to 87.5% in those without LVSI (P<0.001). Patients with elevated pretreatment CA-125 levels had 84.4% OS compared to 89.4% for those with normal CA-125 values (P<0.001). Multivariate analysis demonstrated that Black vs. White race (HR=1.32, 95% CI, 1.10-1.59; P<0.003), Southern vs Northeast Region (HR=1.23, 95% CI, 1.07-1.40; P<0.003), mucinous vs serous histology (HR=1.67, 95% CI, 1.41-1.98; P<0.001), clear cell vs serous histology (HR=1.26, 95% CI, 1.08-1.46; P<0.003), stage IC vs IA (HR=1.50, 95% CI, 1.35-1.67; P<0.001), LVSI (HR=1.82, 95% CI, 1.35-2.45; P<0.001), grade 3 vs 1 (HR=2.21 95% CI, 1.87-2.61, P<0.001) and elevated vs normal CA-125 (HR=1.50, 95% CI, 1.31-1.71, P<0.001) were independent predictors for worse survival. <h3>Conclusions:</h3> Our data suggest that pretreatment CA-125 is an independent prognostic factor in women with stage I epithelial ovarian cancer. Other predictors of survival include race, region, sub-stage, cell type, grade, and LVSI.

RECIST/CA-125 progression-free survival and the role of CA-125 surveillance in the phase III PAOLA-1/ENGOT-ov25 trial evaluating maintenance olaparib plus bevacizumab in patients with newly diagnosed advanced high-grade ovarian carcinoma

<h3>Objectives:</h3> In the PAOLA-1/ENGOT-ov25 primary analysis (NCT02477644), adding the PARP inhibitor olaparib to maintenance bevacizumab (bev) after first-line platinum-based chemotherapy with bev led to a significant progression-free survival (PFS) benefit vs placebo (pbo) + bev in patients (pts) with advanced high-grade ovarian cancer (HGOC), using modified RECIST v1.1 criteria (HR 0.59; 95% CI 0.49-0.72; <i>P</i><0.001; median PFS 22.1 vs 16.6 months) (Ray-Coquard <i>et al. NEJM</i> 2019). Limited evidence supports use of serum CA-125, a surrogate biomarker for progression, to detect relapse in pts receiving PARP inhibitor maintenance therapy. We evaluated RECIST/CA-125 progression and CA-125 surveillance in PAOLA-1. <h3>Methods:</h3> Pts with newly diagnosed, FIGO stage III-IV HGOC in response after platinum-based chemotherapy plus bev received bev (15 mg/kg q3w for 15 months) + olaparib (300 mg bid for 24 months) or pbo. Scans were performed every 24 weeks, or every 12 weeks if there was evidence of clinical or CA-125 progression. CA-125 levels were assessed every 12 weeks. Time to RECIST or CA-125 progression or death was a secondary endpoint; RECIST/CA-125 progression by biomarker status, response to initial therapy and CA-125 level at baseline were explored. <h3>Results:</h3> 537 pts were randomized to olaparib + bev and 269 to pbo + bev with median follow-up for PFS by RECIST/CA-125 of 24.2 vs 24.7 months (DCO 22 March 2019). In the ITT population, the benefit provided by olaparib + bev vs pbo + bev for PFS by RECIST/CA-125 (HR 0.58; 95% CI 0.48-0.70; <i>P</i><0.0001; median PFS 22.1 vs 15.4 months) was consistent with the primary analysis of PFS by RECIST. Of 462 pts with RECIST progression (ITT), 39% had RECIST progression alone and 45% had CA-125 progression more than 7 days before RECIST progression, with a median 2.4 months between CA-125 and RECIST progression (Table). In subgroup analyses, 49% of t<i>BRCA</i>m pts and 45% of HRD-positive pts had RECIST progression alone compared with only 37% of HRD-negative pts. 42% of pts with NED or CR had RECIST progression alone compared with 33% of pts with PR. 44% of pts with normal baseline CA-125 levels had RECIST progression alone compared with only 17% of pts with abnormal baseline CA-125 levels (<i>P</i><0.001). The rate of PFS events by RECIST/CA-125 was higher for pbo + bev vs olaparib + bev (74% vs 53%) (ITT). Of pts with RECIST progression, a similar proportion in each treatment arm had RECIST progression alone, including in subgroup analyses by biomarker status and response to initial therapy. <h3>Conclusions:</h3> Median PFS and HRs were consistent when progression was assessed by either RECIST or RECIST/CA-125 in PAOLA-1. Scans appear particularly important for detecting progression in HRD-positive pts, t<i>BRCA</i>m pts or pts with normal CA-125 levels at baseline as CA-125 levels did not seem to predict relapse in these pts. Results suggest that CA-125 surveillance alone may be sufficient to detect progression in most pts with abnormal baseline CA-125 levels when starting maintenance therapy.

The influence of age, race, and histology on the expression of preoperative CA-125 in stage I epithelial ovarian cancer patients

Objectives: To determine the expression of CA-125 in stage I epithelial ovarian cancer patients by demographic and clinicopathologic factors. Methods: Data were obtained from the National Cancer Database (NCDB PUF 2016) between 2004 and 2015. CA-125 results were reported as abnormal if they were ≥35 Units/mL before treatment. The proportions of abnormal and normal CA-125 levels were compared between groups using Chi-square test. A multivariate logistic regression analysis was used to determine adjusted odds ratio (aOR) and 95% confidence interval (CI). Results: Of 14,912 patients with stage I epithelial ovarian cancer, the median age was 55 years (range 18-90). Whites, Hispanics, Asians and Blacks comprised 83.2%, 5.4%, 4.9%, and 4.5% respectively. Stage IA, IB, IC, and NOS were found in 49.9%, 4.9%, 41.1%, and 4.0% of patients, respectively. The distribution by histology included 36.1%, 24.5%, 19.9%, or 19.5% with endometrioid, serous, clear cell, or mucinous carcinoma and 24.2%, 20.6%, 45.5%, or 9.7% with grade 1, 2, 3, or missing, respectively. An elevated CA-125 level (≥35 Units/mL) was observed in 70.9% of stage I epithelial ovarian cancer patients. The proportion with elevated relative to normal CA-125 did not vary by age or race. A total of 71.4% of older patients (≥50 years) had abnormal CA-125 levels compared to 70.0% of the younger cohort (P=.085). 68.2%, 72.6%, 70.9% or 70.2% of Blacks, Asians, Whites or Hispanics had abnormal CA-125 levels, respectively (P=0.14). Black and Hispanic patients had higher proportions with missing or not tested CA-125 (36.1% and 31.6%) compared with 27.5% and 27.3% of Whites and Asians (P Download : Download high-res image (113KB) Download : Download full-size image Conclusions: Compared to Whites, Blacks and Hispanics were less likely to have CA-125 testing. Over 70% of patients with stage I epithelial ovarian cancer have elevated preoperative CA-125 levels. Women with mucinous and clear cell carcinoma, lower sub-stage, and grade 1 disease were more likely to have normal CA125 levels.