Normal CA-125 Levels Research Articles

Effectiveness, safety, and biomarker analysis of lenvatinib plus toripalimab as chemo-free therapy in advanced intrahepatic cholangiocarcinoma: a real-world study

BackgroundTreatment options for advanced intrahepatic cholangiocarcinoma (ICC) are currently limited. Chemo-containing regimens are the mainstay treatments but associated with notable toxicity, poor tolerance, and reduced compliance, necessitating exploration of alternative therapies. Lenvatinib plus PD-1 inhibitors has shown substantial clinical activity in preliminary studies. This study aimed to assess the effectiveness and safety of lenvatinib plus toripalimab (a novel PD-1 antibody) as chemo-free therapy in advanced ICC.MethodsThis retrospective study included consecutive advanced ICC patients receiving lenvatinib plus toripalimab between February 2019 and December 2023. The main outcomes were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and safety. Prognostic factors and exploratory analyses for genetic alternations were also conducted.ResultsA total of 78 patients were included, with a median follow-up of 25.9 months. Median OS and PFS were 11.3 (95% CI: 9.5–13.1) and 5.4 (95% CI: 3.8–7.0) months, respectively. ORR was 19.2% and DCR was 75.6%. The incidence of grade 3 or 4 adverse events (AEs) was 50.0%, with no grade 5 AEs reported. Patients with normal baseline CA19-9 levels exhibited a higher ORR (p = 0.011), longer PFS (11.5 versus 4.6 months; HR 0.47; p=0.005), and OS (21.0 versus 9.7 months; HR 0.43; p=0.003). The presence of IDH1 mutations correlated with increased ORR (60.0% versus 8.9%, p=0.016).ConclusionLenvatinib plus toripalimab represents an effective and well-tolerated chemo-free therapeutic option for advanced ICC. Baseline CA19-9 levels and IDH1 mutations may serve as predictive treatment-related biomarkers.

A dual-center study: can ultrasound radiomics differentiate type I and type II epithelial ovarian cancer patients with normal CA125 levels?

CA125 is recommended by many countries as the primary screening test for ovarian cancer. But there are patients with ovarian cancer having normal CA125. We hope to identify the types of EOC with normal CA125 levels better by building a refined model based on the ultrasound radiomics, thus providing precise medical treatment for patients. We included 58 patients with EOC with normal CA125 from 2 centres, who were confirmed by preoperative ultrasound and pathology. We extracted 1130 radiomics features based on the tumour's region of interest from the most typical ultrasound image of each patient. We selected radiomics and clinical features by LASSO and logistic regression to construct Rad-score and clinical models, respectively. Receiver operating characteristic curves judged their test efficacy. On the basis of the combined model, we developed a nomogram. Area under the curves (AUCs) of 0.93 and 0.83 were achieved in both the training and test groups for the combined model. There were similar AUCs between the Rad-score and clinical models of 0.82 and 0.80, respectively. By analysing the calibration curves, it was determined that the nomogram matched actual observations in the training cohort. Ultrasound radiomics can differentiate type I and type II EOC with normal CA125 levels. This study is the first to focus on EOC cases with normal level of CA125. The subset of patients constituting 20% of the disease population may require more refined radiomics models.

Exploring metastasis and recurrence patterns in low-risk grade 3 endometrial cancer: A multicenter retrospective cohort study

ObjectiveFemales with low-risk endometrial cancer typically have low lymph node metastasis risk and promising prognosis without lymphadenectomy. However, the impact of grade 3 endometrial cancer on nodal involvement, recurrence, and prognosis within this specific subgroup remains unclear. Therefore, in this study, we aimed to investigate the prognosis, patterns of metastasis, and recurrence in a subgroup of females with grade 3 early-stage low-risk endometrioid endometrial cancer. MethodsWe identified patients from the endometrial cancer cohorts of seven institutional hospitals. The study included patients who underwent hysterectomy between January 2013 and December 2021 with preoperative endometrioid histological type, less than half myometrial invasion, no tumor spread outside the corpus on imaging, normal CA-125 level, and histological grade 3. The clinicopathological characteristics and survival outcomes of the patients were collected. Recurrence-free survival was estimated using the Kaplan–Meier method and compared using the log rank test. ResultsOverall, 36 patients were included in this analysis. Of the 33 patients who underwent lymphadenectomy, 1 (1/33, 3.0 %) had lymph node metastasis and 27 (75.0 %) received adjuvant therapy. At a median follow-up of 58 months, three females (8 %) had recurrence and all cases involved lymph nodes. The 5-year recurrence-free survival was 88.7 %. No significant difference was observed in the recurrence-free survival between females who did and did not undergo lymphadenectomy (p = 0.554). ConclusionFemales diagnosed with low-risk grade 3 endometrial cancer typically have favorable prognosis. However, lymph node metastasis and recurrence risks still exist, with all recorded instances of recurrence involving lymph nodes.

Prognosis and predictive factors of conversion surgery for initially unresectable advanced colorectal cancer

PurposeThe aim of this study was to report the outcomes of conversion surgery for initially unresectable advanced colorectal cancer and to identify factors that enable successful conversion surgery.MethodsWe compared the outcomes of patients with colorectal cancer with distant metastases, including extrahepatic metastases, who underwent upfront surgery, neoadjuvant chemotherapy, conversion surgery, and chemotherapy only at our department from 2007 to 2020. In addition, factors influencing the achievement of conversion surgery in patients who were initially unresectable were examined in univariate and multivariate analyses.ResultsOf 342 colorectal cancer patients with distant metastases treated during the study period, 239 were judged to be initially unresectable, and 17 (conversion rate: 7.1%) underwent conversion surgery. The prognosis for the conversion surgery group was better than that of the chemotherapy only group but worse than that of the upfront surgery group. In the conversion surgery group, the recurrence-free survival after resection was significantly shorter than that upfront surgery group and neoadjuvant chemotherapy group, and no patients have been cured. Among patients who were initially unresectable, left-sided primary cancer and normal CA19-9 level were identified as independent factors contributing to the achievement of conversion surgery in a multivariate analysis.ConclusionsAlthough relapse after conversion surgery is common, and no patients have been cured thus far, overall survival was better in comparison to patients who received chemotherapy only. Among unresectable cases, patients with left-sided primary cancer and normal CA19-9 levels are likely to be candidates for conversion surgery.

Abstract PO3-20-09: METACHRONOUS METAPLASTIC BREAST CARCINOMA IN A 55-YEAR-OLD PATIENT WITH SEROUS OVARIAN CARCINOMA

Abstract Metaplastic breast carcinoma is a rare histologic subtype of breast carcinoma, accounting for only 0.2 to 2% of all breast cancers. It is comprised of a heterogeneous histology involving mesenchymal and epithelial components. Metaplastic breast carcinoma usually harbors a triple-negative phenotype, but carries a worse prognosis compared to other breast cancer subtypes. Due to its unique histopathological and molecular characteristics, there has been limited data on the optimal management of metaplastic breast carcinoma. Moreover, the presence of a secondary breast neoplasm in the background of a prior ovarian carcinoma represents a diagnostic and therapeutic challenge. We report a case of a 55-year-old female with a previous history of serous ovarian carcinoma six years ago, who presented with an enlarging right breast mass. Digital mammography showed a right retro-areolar mass, 5.7 x 4.8 x 5.4 cm, BIRADS 4C. Initial biopsy done showed presence of atypical cells in a background of cystic change. The patient underwent modified radical mastectomy with incision biopsy and frozen section. Final histopathologic diagnosis was consistent with metaplastic breast carcinoma, mixed epithelial and mesenchymal type, Nottingham grade 2, with no lymphovascular invasion identified, pT2N0. Tumor was ER negative, PR negative, Her 2 neu negative, with Ki-67 of 10% on immunohistochemistry. She then underwent adjuvant treatment with 6 cycles of paclitaxel and carboplatin. Six years prior, the patient was likewise diagnosed with high-grade serous ovarian carcinoma. She had total abdominal hysterectomy with bilateral salpingo-oophorectomy and adjuvant chemotherapy with 6 cycles of Paclitaxel and Carboplatin was given. She had recurrence in the paraaortic lymph node after 3 years and underwent cytoreductive surgery with excision of nodule and hyperthermic intraperitoneal chemotherapy with cisplatin. Currently, the patient has no evidence of disease in the recent positron emission tomography scan, with normal serum CA-125 level. The current standard of care for metaplastic breast carcinoma follows that of triple-negative breast cancer. However, previous literature has shown that metaplastic breast carcinoma is more chemo-refractory compared to triple-negative breast cancer, with more response seen with taxane-based chemotherapy. Due to poor response rates to neoadjuvant chemotherapy, surgical management for early-stage disease is warranted. Targeting molecular alterations is necessary to improve the prognosis of this subtype. Genomic features of homologous recombination deficiency were also found to be more prevalent in metaplastic breast cancer, thus genomic testing is warranted, especially in the setting of a prior history of ovarian carcinoma. Citation Format: Raye Angeli Abella, Carlos Dy. METACHRONOUS METAPLASTIC BREAST CARCINOMA IN A 55-YEAR-OLD PATIENT WITH SEROUS OVARIAN CARCINOMA [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-20-09.

Effect of glycotoxicity and lipotoxicity on carbohydrate antigen 19 − 9 in the patients with diabetes

ObjectivesIn comparison to the subjects without diabetes, a greater concentration of serum carbohydrate antigen 19 − 9 (CA 19 − 9) was observed in the subjects with diabetes. Nevertheless, since the occurrence of abnormal CA 19 − 9 is not widespread among the whole diabetic population, this phenomenon has not attracted enough attention. The prevalence of abnormal CA 19 − 9 in hospitalized patients with diabetes was the focus of our research.MethodA total of 385 subjects with diabetes and 200 controls were enrolled and all had been tested the CA19-9 levels. Cases of cancers were excluded through examination and followup for 1 year.ResultsWe found that the rate of patients with abnormal CA19-9 level was 8.3%. The rate of patients with abnormal CA19-9 level was 14.0% in the HbA1c ≥ 9% group, and 3.0% in the HbA1c < 9% group, 2.5% in the control group. There was no significant difference in the HbA1c < 9% group and the control group. A significant correlation between serum CA19-9 and both HbA1c and total cholesterol was observed, yet no difference in CRP level was observed between subjects with normal CA19-9 level and subjects with abnormal CA19-9 level. However, a significant difference in fasting C-peptide levels was observed between the two groups, p = 0.039.ConclusionThe percentage of patients with diabetes exhibiting elevated CA19-9 level is 14% in the HbA1c ≥ 9% diabetic patients, much higher than expected. The underlying mechanism may be related to islet injury caused by glycotoxicity and lipotoxicity. Strengths and limitations of the studyWe studied the rate of hospitalized diabetic patients with elevated CA 19 − 9 which were characterized with poorly controlled blood glucose. We found that the elevation of CA 19 − 9 was unexpectedly high in diabetic inpatients without development to cancer. The limitation of this study is that the underlying mechanism is not sufficiently studied.

Clinical Utility of the Combined Use of CA19-9 and DUPAN-2 in Pancreatic Adenocarcinoma

PurposePancreatic ductal adenocarcinoma (PDAC) patients with normal carbohydrate antigen (CA) 19-9 levels can have early-stage cancer or advanced cancer without elevation of CA19-9 level; estimating their malignant potential is difficult. This study investigated the clinical utility of the combined use of preoperative CA 19-9 and Duke pancreatic monoclonal antigen type 2 (DUPAN-2) levels in patients with PDAC.MethodsPatients who underwent curative-intent surgery for PDAC between November 2005 and December 2021 were investigated. Eligible patients were classified into four groups based on these two markers. Among patients with normal CA19-9 levels, those with normal and high DUPAN-2 levels were classified into normal/normal (N/N) and normal/high (N/H) groups, respectively. Among patients with high CA19-9 levels, those with normal and high DUPAN-2 levels were classified into high/normal (H/N) and high/high (H/H) groups, respectively. Survival rates were compared between the groups.ResultsAmong 521 patients, the N/N, N/H, H/N, and H/H groups accounted for 25.0%, 10.6%, 35.1%, and 29.4% of patients, respectively. The proportions of resectable PDAC in the N/N and H/N groups (71.5% and 66.7%) were significantly higher than those in the N/H and H/H groups (49.1% and 54.9%) (P < 0.01). The 5-year survival rates in the N/N, N/H, H/N, and H/H groups were 66.0%, 31.1%, 34.9%, and 29.7%, respectively; the rate in the N/N group was significantly better than those in the other three groups (P < 0.0001, P < 0.0001, and P < 0.0001, respectively).ConclusionsOnly patients with normal CA19-9 and DUPNA-2 values should be diagnosed with early-stage PDAC.

Large Ovarian Cyst - Laparoscopic Entry: A Case Report

This report is aimed at introducing a simple technique to improve safety in drainage of large ovarian cyst managed with laparoscopic techniques. A 31-year-old, nulliparous woman, presented with a massive unilocular ovarian cyst measuring 22.48 cm in height, 18.92 cm in transverse axis, and 8.03 cm antero posteriorly. She had a normal CA125 level. Entry was done with the open technique (Hasson's) at the midpoint between umbilicus and the xiphisternum (Lee Huang). Through this opening the cyst wall was separated by blind dissection to avoid damage to cyst wall. Then the cyst contents were drained with a Veress needle. Troche was inserted through the same incision and pneumoperitoneum was created allowing a routine cystectomy. The critical step in managing large cysts is safe entry and inducing pneumoperitoneum. Using a simple technique, could improve safety resulting in successful a successful outcome of laparoscopic techniques for large ovarian cysts.

The relationship between clinical and pathological findings and FDG - PET uptake in metastatic colorectal cancers.

In metastatic colorectal cancer (mCRC), the genetic structure and cell metabolism of the primary tumor lesion might be different from metastatic lesions. It is thought that cell-level glucose metabolism may differ due to the difference in RAS wild and mutant mCRC patients' prognosis. In this study, we aimed to compare 2-deoxy-2-[fluorine-18]-fluoro-D-glucose Positron Emission Tomography (18F-FDG PET/CT) uptake levels for KRAS mutation status and primary-metastatic tumor localization. Our study is a retrospective cohort analysis that included RAS mutation status study and staging-oriented 18F-FDG PET/CT conducted on mCRC patients. There was no significant relationship between metastasis and primary tumor maximum Standardized uptake value (SUVmax) values according to the KRAS mutational status (P > 0.05). Patients with liver metastasis along with mutant BRAF mutation status had significantly higher SUVmax values in PET-CT scans (P = 0.04). There was a negative correlation between SUVmax values of lung metastases and overall survival (r = -0.35, P = 0.04). Patients with high carcinoembryonic antigen (CEA) levels had significantly higher SUVmax values of lung metastasis than patients with normal CEA levels (P = 0.009). Patients with high CA19-9 levels had significantly higher SUVmax values of liver, peritoneal, and bone metastasis than patients with normal CA19-9 levels (P = 0.002, P = 0.001, P = 0.004, respectively). There was no significant correlation between SUVmax values of metastasis and Lactate dehydrogenase (LDH) values. Liver metastasis of right-sided mCRCs had significantly higher SUVmax values (P = 0.03). We could not demonstrate a significant association between KRAS mutation and SUVmax values of PET scan in primary or metastatic tumor sites in advanced CRC.

Role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography in the detection of recurrence and peritoneal metastasis from ovarian cancer in correlation with cancer antigen-125 tumor marker levels

BackgroundThe chronic nature of ovarian cancer and disease recurrence has a considerable impact on the assessment of follow-up strategies and treatment planning for both oncologists and radiologists. It is imperative to conduct adequate follow-up in ovarian cancer to detect and treat recurrence as early as possible. Presently, surveillance of patients with this malignancy involves the combination of serial CA-125 assay and diverse imaging procedures, yet normal CA-125 levels cannot entirely rule out disease relapse. PET/CT provides whole-body functional imaging that does not necessities contrast injection, and allows for precise diagnosis and restaging of patients with suspected ovarian cancer recurrence, thereby strongly impacting disease management decisions. Our study aims to evaluate the value of FDG-PET/CT as a follow-up imaging tool in detecting and localizing recurrence of ovarian cancer, in conjunction with CA-125 tumor markers.ResultsIn our study, it was demonstrated that recurrent disease manifested in FDG-PET/CT in 24 cases, with 9 of those cases exhibiting CA-125 levels within the normal range. There were two instances of false negative results and one instance of false positive results in FDG-PET/CT. Additionally, three cases were found to be free of disease relapse in FDG-PET/CT and exhibited normal CA-125 levels throughout the follow-up period (true negative). The prevalence of disease recurrent sites was 12% for local recurrence, 60% for peritoneal metastasis, 64% for nodal deposits and 28% for distant metastatic disease. The accuracy of FDG-PET/CT was 88.8%, with a sensitivity of 91.3% and specificity of 75%. Furthermore, FDG-PET/CT showed a positive predictive value of 95.5% and a negative predictive value of 60.3%.ConclusionsPET/CT imaging provides a comprehensive and functional view of the entire body, which can accurately diagnose and restage cases with ovarian cancer recurrence. This approach plays a critical role in identifying peritoneal carcinomatosis and is considered a more dependable method than CA-125 tumor markers for detecting and monitoring ovarian cancer recurrence. Additionally, PET/CT imaging has the potential to decrease the number of second-look laparotomies and can thus significantly impact the management plan.

Study protocol for prospective multi-institutional phase III trial of standard of care therapy with or without stereotactic ablative radiation therapy for recurrent ovarian cancer (SABR-ROC)

BackgroundEfforts have been made to investigate the role of salvage radiotherapy (RT) in treating recurrent ovarian cancer (ROC). Stereotactic ablative radiation therapy (SABR) is a state-of-the-art therapy that uses intensity modulation to increase the fractional dose, decrease the number of fractions, and target tumors with high precision.MethodsThe SABR-ROC trial is a phase 3, multicenter, randomized, prospective study to evaluate whether the addition of SABR to the standard of care significantly improves the 3-year overall survival (OS) of patients with ROC. Patients who have completed the standard treatment for primary epithelial ovarian cancer are eligible. In addition, patients with number of metastases ≤ 10 and maximum diameter of each metastatic site of gross tumor ≤ 5 cm are allowed. Randomization will be stratified by (1) No. of the following clinical factors met, platinum sensitivity, absence of ascites, normal level of CA125, and ECOG performance status of 0–1; 0–3 vs. 4; (2) site of recurrence; with vs. without lymph nodes; and (3) PARP inhibitor; use vs. non-use. The target number of patients to be enrolled in this study is 270. Participants will be randomized in a 1:2 ratio. Participants in Arm 2 will receive SABR for recurrent lesions clearly identified in imaging tests as well as the standard of care (Arm 1) based on treatment guidelines and decisions made in multidisciplinary discussions. The RT fraction number can range from 1 to 10, and the accepted dose range is 16–45 Gy. The RT Quality Assurance (QA) program consists of a three-tiered system: general credentialing, trial-specific credentialing, and individual case reviews.DiscussionSABR appears to be preferable as it does not interfere with the schedule of systemic treatment by minimizing the elapsed days of RT. The synergistic effect between systemic treatment and SABR is expected to reduce the tumor burden by eradicating gross tumors identified through imaging with SABR and controlling microscopic cancer with systemic treatment. It might also be beneficial for quality-of-life preservation in older adults or heavily treated patients.Trial registrationThis trial was registered at ClinicalTrials.gov (NCT05444270) on June 29th, 2022.

The role of PET/CT with fluorine-18-deoxyglucose in the detection of relapsed serous ovarian cancer in patients with normal serum CA125 levels.

To assess the role of the positron emission tomography with fluorine-18-deoxyglucose (PET/CT) in the detection of recurrent serous ovarian cancer in patients with normal serum CA125 level. Thirty-one patients with suspected recurrent serous ovarian cancer with normal (< 35 IU/mL) serum CA125 level and no prior recurrence underwent PET/CT imaging. The results of the PET/CT were analyzed considering clinical data of the patients, histological diagnosis and 6 months follow-up. The patients were referred to the PET/CT due to suspected relapse in imaging tests (CT - 11 cases, US - 3 cases, MRI - 2 cases; n = 16; 51.6%), clinical examination (n = 4; 12.9%) and clinical symptoms (n = 11; 35.5%). The recurrent serous ovarian cancer was present in 16 patients (51.6%). In 9 these cases (56.3%) the recurrences were diagnosed in patients aged 51-70 years. In 15 cases (93.8%) the recurrences were diagnosed within 24 months after treatment. There were 15 true positive (48.4%), 12 true negative (38.7%), 3 false positive (9.7%) and 1 false negative (3.2%) PET/CT results. Sensitivity, specificity, positive and negative predictive value of the PET/CT were calculated as 93.8% (95% CI, 86.1-97.4%), 80.0% (95% CI, 69.7-88.9%), 83.3% (95% CI, 74.3-90.4%) and 92.3% (95% CI, 84.2-98.3%), respectively. In patients with a diagnosis of complete remission after treatment for serous ovarian cancer, even a multifocal recurrence may occur during follow up despite normal serum CA125 levels. Our results showed a usefulness of the PET/CT in detecting and differentiating malignant from benign lesions in patients with normal serum CA125 levels but inconclusive results in other imaging tests. We observed false results of the PET/CT for lesions in parotid gland, mesorectal adipose tissue and mediastinal lymph nodes.

Fortuitously detected primary ovarian carcinoid tumor: A case report.

Carcinoid tumors, derived from the cells of the disseminated neuroendocrine system, are rare, slow-growing neuroendocrine neoplasms that display a relatively indolent disease course. The majority of carcinoids are found within the gastrointestinal tract and bronchopulmonary system. Primary ovarian carcinoids are rare and account for merely 1% of all carcinoid tumors. We describe our experience of a rare case of primary ovarian carcinoid, presenting as chronic constipation, with no other carcinoid symptoms such as flushing, diarrhea, and wheezing. A 51-year-old postmenopausal woman with chronic constipation visited the clinic for routine check-up of her preexisting uterine fibroids. She had undergone hemorrhoidectomy 3 years ago. Physical examination revealed a soft abdomen without direct or rebound tenderness. Transvaginal ultrasonography revealed two subserosal fibroids, which had increased in size compared with previous ultrasonographic findings. A 3 cm hyperechoic mass was also detected in the right ovary. Her blood and urine tests were unremarkable, with no ascites in the pelvic cavity. She had a normal CA-125 level of 5.5 units/mL. The patient underwent a robot-assisted hysterectomy and right salpingo-oophorectomy because of enlarging fibroids and the right ovarian mass. Subsequently, based on the pathological and immunohistochemical findings, she was diagnosed with a primary ovarian carcinoid. The mass consisted of the insular and trabecular types of tumor cells. It was positive for pan-cytokeratin and synaptophysin, and the Ki-67 proliferation index was less than 1%. A follow-up positron emission tomography-computed tomography revealed no distant metastasis. Six months postoperatively, the patient was doing well without any signs of recurrence. Primary ovarian carcinoids without teratoma components are rare. It is crucial to make an accurate diagnosis based on the immunohistochemical staining results. Diagnosis in the early stages of the disease are associated with a favorable prognosis, but regular follow-up is mandatory.

ASO Author Reflections: Prognostic Role of Preoperative Duke Pancreatic Monoclonal Antigen Type 2 Values in Patients with Pancreatic Cancer: Focusing on the Usefulness in Patients with Normal CA19-9.

Pancreatic cancer (PC) is one of the most aggressive cancer types, and carbohydrate antigen (CA) 19-9 has been the most useful biomarker for its surveillance and prognosis prediction. However, CA19-9 may not be sufficiently prognostic in some patients, such as Lewis antigen-negative phenotype (Le[a-b-]) patients who secrete little or no CA19-9. Duke pancreatic monoclonal antigen type 2 (DUPAN-2) has been proposed as a complementary marker to CA19-9 in PC patients, but its utility in Le(a-b-) patients has only been reported in a limited number of cases. In a retrospective analysis of 224 PC patients who underwent surgery, the present study investigated the utility of DUPAN-2 in combination with CA19-9. The study subjects were divided into three groups based on their CA19-9 and DUPAN-2 levels. The normal CA19-9/high DUPAN-2 group had significantly larger tumors and a higher frequency of microscopic vascular invasion, perineural invasion, and recurrence than the normal CA19-9/normal DUPAN-2 group. Both the disease-free survival and disease-specific survival (DSS) of patients in the normal CA19-9/high DUPAN-2 group were significantly shorter than those in the normal CA19-9/normal DUPAN-2 group, and comparable with those in the high CA19-9 group. The results suggest that DUPAN-2 may be useful as a complementary biomarker to CA19-9 in PC, especially in patients who have normal CA19-9 levels. However, since this was a single-center, retrospective study, multicenter studies are needed to confirm the findings and determine the optimal cut-off value for patients with normal CA19-9 levels.

A cross-sectional study of 73,390 women without ovarian cancer and the effect of age and benign gynecological diseases on serum CA125 levels.

e17500 Background: As an important tumor marker for follow-up and prognosis of ovarian cancer, CA125 is not suitable as a screening indicator due to its frequent elevation in many physiological or pathological condition, thus women are often puzzled by unaccountably elevated levels of CA125. While we have known that the CA125 level is differed by age and benign gynecological diseases, the specific trend of CA125 level changes is still not clear. We hope that this study will contribute to a more accurate and individual interpretation of CA125 by evaluating the baseline levels of CA125 in healthy women of different ages and analysis the association between benign gynecological diseases and CA125 level. Methods: This was a cross-sectional study enrolled 73390 women without ovarian cancer from January 2016 to December 2021 in three health examination centers. We have assessed the distribution of CA125 levels in different age groups and analyzed the variation trend of CA125 levels by age among women with normal ultrasonic results, as well as performed the correlation analysis between several benign gynecological diseases and CA125 levels. Results: 55422 women with normal ultrasonic results and CA125 level &lt;200U/mL were included in the analysis of variations in CA125 depending on age. We observed CA125 levels were linearly associated with age (R2=0.0503, p&lt;0.0001). Using the group &lt;30 years as a baseline, average CA125 levels decreased by 3.4%, 10.1%, 42.6%, 40.5%, 31.8%, and 20.3% by every 10 years. With the increase of age, the downward trend of CA125 began to reverse at the age of 60, and it showed significantly difference between each adjacent subgroup (p&lt;0.05). 8630 women were selected with abnormal ultrasonic results, we observed that CA125 was lower in women with uterine effusion, higher in endometrial hyperplasia, endometrial polyps, hydrosalpinx, ovarian cyst, adenomyosis and uterine fibroids. Age and all those diseases demonstrated possible associations (p&lt;0.05) with CA125 levels ≥35U/ml in univariable logistic regressions. Multivariable analysis identified that ovarian cyst (p&lt;0.001), adenomyosis (p&lt;0.001) and uterine fibroids (p=0.018) were still significantly associated with abnormal CA125 level. Conclusions: With the increase of age, CA125 level generally showed a downward trend, but there is a slight increase in CA125 after age 60. Ovarian cyst, adenomyosis and uterine fibroids demonstrated significant associations with abnormal CA125 level. [Table: see text]

Extraordinary clinical response to ibrutinib in low-grade ovarian cancer guided by organoid drug testing

Low-grade serous ovarian cancer (LGSOC) typically responds poorly to standard platinum-based chemotherapy and new therapeutic approaches are needed. We describe a remarkable response to targeted therapy in a patient with platinum-resistant, advanced LGSOC who had failed standard-of-care chemotherapy and two surgeries. The patient was in rapid decline and entering hospice care on home intravenous (i.v.) opioid analgesics and a malignant bowel obstruction requiring a G-tube. Genomic analysis of the patient’s tumor did not indicate obvious therapeutic options. In contrast, a CLIA-certified drug sensitivity assay of an organoid culture derived from the patient’s tumor identified several therapeutic choices, including Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib, as well as the EGFR inhibitors afatinib and erlotinib. Following off-label administration of daily ibrutinib as monotherapy, the patient had an exceptional clinical turnaround over the following 65 weeks with normalization of CA-125 levels, resolution of the malignant bowel obstruction, halting of pain medications, and improvement of performance status from ECOG 3 to ECOG 1. After 65 weeks of stable disease, the patient’s CA-125 levels began to rise, at which point the patient discontinued ibrutinib and began taking afatinib as monotherapy. The patient’s CA-125 levels remained stable for an additional 38 weeks but due to anemia and rising CA-125 levels, the patient switched to erlotinib and is currently being monitored. This case highlights the clinical utility of ex vivo drug testing of patient-derived tumor organoids as a new functional precision medicine approach to identify effective personalized therapies for patients who have failed standard-of-care treatments.

Clinical features and images of malignant lymphoma localized in the pancreatic head to differentiate from pancreatic ductal adenocarcinoma: a case series study

BackgroundPathological examination by endoscopic ultrasonography–guided fine-needle aspiration (EUS-FNA) has been reported to be useful in diagnosing pancreatic malignant lymphoma (ML), but some ML cases are difficult to be differentiated from pancreatic ductal adenocarcinoma (PDAC).MethodsThis retrospective study included 8 patients diagnosed with ML that had a pancreatic-head lesion at initial diagnosis and 46 patients with resected PDAC in the pancreatic head between April 2006 and October 2021 at our institute. ML and PDAC were compared in terms of patients’ clinical features and imaging examinations.ResultsThe median tumor size was larger in ML than in PDAC (45.8 [24–64] vs. 23.9 [8–44] mm), but the median diameter of the caudal main pancreatic duct (MPD) was larger in PDAC (2.5 [1.0–3.5] vs. 7.1 [2.5–11.8] mm), both showing significant differences between these malignancies (both, P < 0.001). In the analysis of covariance, MLs showed a smaller caudal MPD per tumor size than PDACs, with a statistical difference (P = 0.042). Sensitivity and specificity using sIL-2R ≥ 658 U/mL plus CA19-9 < 37 U/mL for the differentiation of ML from PDAC were 80.0% and 95.6%, respectively.ConclusionsDiagnosing pancreatic ML using cytohistological examination through EUS-FNA can be difficult in some cases. Thus, ML should be suspected if a patient with a pancreatic tumor has a small MPD diameter per tumor size, high serum sIL-2R level, normal CA19-9 level. If the abovementioned features are present and still cannot be confirmed as PDAC, re-examination should be considered.

Correlation between clinical characteristics of colorectal cancer and nutritional status in patients undergoing surgery

Background: The incidence of colorectal cancer in Indonesia reaches 12.8 per 100,000 adult population and is the cause of 9.5% of cancer deaths. 40–80% of all colorectal cancer patients are malnourished. This study aims to determine the prevalence of nutritional status in colorectal cancer and the correlation between clinical characteristics of colorectal cancer and nutritional status in patients undergoing surgery. Methods: This research is an observational study with a cross sectional method. The reachable population of this study was colorectal cancer patients who underwent surgery at dr. Cipto Mangunkusumo Hospital, Jakarta and admission will occur from September-December 2022 with predetermined inclusion and exclusion criteria. The instrument used is the Mini Nutritional Assessment (MNA)—bivariate data analysis using Chi-square followed by a multivariate logistic regression test. Results: There were 71 patients diagnosed with colorectal cancer at RSUPN dr. Cipto Mangunkusumo, in the September-December 2022 period, will undergo surgery. Clinical characteristics of colorectal cancer patients showed that most patients were 64-78 years old (57.7%) and male (52.1%). For clinical stages, it can be seen that the majority of patients have stages III and IV (78.9%), with a large tumor mass of 1-10.9 cm (76.1%), and the location of the cancer is in the rectum (59.2%) ). The results of CA19-9 levels show that most patients with normal CA19-9 levels (62.0%) and CEA levels were increased (66.2%). While the nutritional status of colorectal cancer, most of them have at risk of being malnourished (52.1%), followed by having malnourished (43.7%). The bivariate test results showed that the tumor size was significant (p &lt;0.05). Conclusion: Most colorectal cancers are at risk of malnourished and there is a statistically strongest correlation between tumor mass and nutritional status in patients undergoing surgery.

Clinicopathological characteristics and treatment outcome of resectable gastric cancer patients with small para-aortic lymph node.

Resectable gastric cancer (GC) patients with small para-aortic lymph node (smaller than 10mm in diameter, sPAN) were seldom reported, and existing guidelines did not provide definite treatment recommendation for them. A total of 667 consecutive resectable GC patients were enrolled. 98 patients were in the sPAN group, and 569 patients without enlarged para-aortic lymph node were in the nPAN group. Standard D2 lymphadenectomy was performed. Neoadjuvant and adjuvant chemotherapy were administrated according to the cTNM and pTNM stage, respectively. Clinicopathological features and prognosis were compared between these two groups. The median size of sPAN was 6 (range, 2-9) mm and the distribution was prevalent in No. 16b1. cN stage (p=0.001) was significantly related to the presence of sPAN. sPAN was both independent risk factor for OS (p=0.031) and RFS (p=0.046) of all patients. The prognosis of patients with sPAN was significantly worse than that of patients with nPAN (OS: p=0.008; RFS: p=0.007). Preoperative CEA and CA19-9 were independent risk factors for prognosis of patients with sPAN. Furthermore, patients in the sPAN group with normal CEA and CA19-9 exhibited acceptable prognosis (5-year OS: 67%; RFS: 64%), while those with elevated CEA or CA19-9 suffered significantly poorer prognosis (5-year OS: 17%; RFS: 17%) than patients in the nPAN group (5-year OS: 64%; RFS 62%) (both p < 0.05). Standard D2 lymphadenectomy should be considered a valid approach for GC patients with sPAN associate to normal preoperative CEA and CA19-9 levels. Patients with sPAN associated to elevated CEA or CA19-9 levels could benefit from a multimodal approach: neoadjuvant chemotherapy; radical surgery with D2 plus lymph nodal dissection extended to No. 16 station.

Clinical Implications of FDG-PET in Pancreatic Ductal Adenocarcinoma Patients Treated with Neoadjuvant Therapy

PurposeTo evaluate the clinical significance of 18F-fluorodeoxyglucose positron emission tomography/computed tomography in patients with pancreatic ductal adenocarcinoma who underwent neoadjuvant therapy. MethodsAmong 285 consecutive patients who underwent pancreatic resection for pancreatic ductal adenocarcinoma between 2015 and 2021, 86 who underwent preoperative 18F-fluorodeoxyglucose positron emission tomography/computed tomography after completion of neoadjuvant treatment were reviewed. Among preoperative factors, including post-treatment maximum standardized uptake value, predictors of early recurrence and poor prognosis were identified using multivariate analysis for decision making in surgery. ResultsNineteen (22%) patients with pancreatic ductal adenocarcinoma demonstrated high maximum standardized uptake (≥ 4.5). High post-treatment maximum standardized uptake (≥ 4.5) predicted early recurrence within 6 months after surgery and correlated with shorter recurrence-free survival. Elevated post-treatment CA19-9 level (> 37 U/ml) and maximum standardized uptake ≥ 4.5 were independent prognostic factors. Post-treatment, a high maximum standardized uptake value indicated a poorer prognosis than a low maximum standardized uptake value in both patients with elevated CA19-9 and normal CA19-9 levels. The median overall survival in patients with elevated post-treatment CA19-9 and high maximum standardized uptake was only 17 months; 67% experienced early recurrence. Dynamic changes in maximum standardized uptake during neoadjuvant therapy were correlated with pathological response to neoadjuvant therapy, but not with radiological response or change in CA19-9 level. ConclusionsPost-treatment assessment using maximum standardized uptake value is useful for stratifying patients with pancreatic ductal adenocarcinoma who will benefit from surgery. Instead of subsequent curative resection, additional neoadjuvant therapy should be considered in patients with a persistently high maximum standardized uptake value.