Elevated Tumor Markers Research Articles

Autopsy diagnosis of diffuse intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (ICC), a severe liver cancer, makes up to 20% of all hepatic malignancies and is difficult to diagnose early due to its often asymptomatic nature. This case report documents a rare presentation of ICC with multiple diffuse nodules not previously recorded in medical literature. A 65-year-old man with no significant medical history presented with back pain, anorexia, and significant weight loss. Elevated tumor markers and enlarged lymph nodes were observed, though imaging did not reveal a primary liver mass. Diagnostic efforts, including computed tomography and positron emission tomography scans and biopsies of lymph nodes and bone marrow, suggested adenocarcinoma of unknown primary origin. A definitive diagnosis was only made post-mortem, revealing multiple diffuse nodules in the liver identified as ICC, marking a rare presentation without a primary mass. This case highlights the diagnostic challenges posed by atypical ICC manifestations, where typical imaging does not indicate a primary mass, delaying diagnosis and treatment. The findings emphasize the importance of considering ICC in differential diagnoses in cases of unknown primary adenocarcinoma with liver involvement. The discovery of ICC with diffusely infiltrative nodules underscores the necessity for comprehensive diagnostic evaluations in patients presenting with nonspecific systemic symptoms and abnormal liver findings.

Pityriasis Rubra Pilaris and underlying malignancy.

A 59-year-old man presented with a five-month history of widespread, salmon-colored, scaly plaques. Skin examination revealed salmon-colored plaques with "islands of sparing" on the trunk and waxy keratoderma on the palms and soles. Histopathology of the lesion showed alternating orthokeratosis and parakeratosis in vertical and horizontal directions, consistent with a diagnosis of pityriasis rubra pilaris (PRP). The patient was unresponsive to methotrexate and Secukinumab. Further evaluation through a computerized tomography scan revealed a presence of air-filled multicystic changes in the upper left lung, accompanied by diffuse pulmonary bullae. Elevated serum tumor markers, including CEA, NSE, and SCC, indicated an underlying acinar-predominant adenocarcinoma, suggesting a paraneoplastic PRP. He was subsequently referred to the oncology department for further management. This report underscores the importance of identifying an underlying malignancy in recalcitrant PRP cases.

Anti‐synthetase syndrome complicated by multifocal tuberculosis: A thought‐provoking differential diagnosis with tumors

AbstractMycobacterium tuberculosis, which mainly affects the lungs but can also invade other systems, presents a diagnostic challenge when co‐existing with autoimmune disease. We report a case of 31‐year‐old Asian woman with anti‐synthetase syndrome who developed abdominal and subcutaneous lumps during treatment, along with elevated tumor markers, raising suspicion of malignancy. Pathological examination revealed M. tuberculosis infection, changing the diagnosis to multifocal extrapulmonary tuberculosis. This case highlights the need for prompt and detailed evaluations, and the importance of broad differential diagnosis.

Monitoring pediatric CNS non-germinomatous germ cell tumors via cerebrospinal fluid circulating tumor DNA.

Accurate molecular and clinical stratification of patients with central nervous system (CNS) non-germinomatous germ cell tumors (NGGCTs) remains challenging, impeding the development of personalized therapeutic approaches. Herein, we investigated the translational significance of cerebrospinal fluid (CSF) circulating tumor DNA (ctDNA) in pediatric NGGCTs to identify characteristic features of CNS NGGCTs and to identify a subset of patients for whom the presence of residual disease is a risk factor and an indicator of shorter progression-free survival (PFS) and overall survival (OS). Medical records of patients with CNS NGGCTs between January 1, 2018 and December 31, 2022 were reviewed retrospectively. The cohort consisted of 11 male and six female patients. Tumor markers were elevated in four of the five people who underwent surgery. The remaining 12 patients were diagnosed with malignant NGGCTs according to elevated tumor markers. Among them, ctDNA before chemotherapy as well as ctDNA clearance were consistently associated with PFS and OS (p<.05). By setting a ctDNA positivity threshold of 6%, patients with high ctDNA (above the threshold) levels, which had limitation due to the selection based on optimal statistic from the survival analysis, had significantly inferior 5-year PFS and OS compared to those with low levels (below the threshold). ctDNA or ctDNA clearance combined with the presence of residual disease predicted significantly worse OS and PFS (p<.05). CSF ctDNA might allow the study of genomic evolution and the characterization of tumors in pediatric NGGCTs. CSF ctDNA analysis may facilitate the clinical management of pediatric NGGCT patients, and aid in designing personalized therapeutic strategies.

Selective Gastrectomy with Knowledge of Gastric Anatomy and Blood Supply are Key to Complete Tumour Removal in Advanced Pseudomyxoma: Single-Centre Experience with 120 Gastrectomies Over 20 Years.

The role of gastrectomy to achieve complete cytoreduction (CCR) for pseudomyxoma peritonei (PMP) is controversial due to uncertain risk/benefit ratio. The outcomes of patients who gastrectomy over a twenty-year period in a high-volume unit are reported. All patients requiring gastrectomy to achieve CCR for appendiceal PMP between 2000 and 2020 were reviewed. Demographics, disease, operative, complication, and survival data were analysed. The first and second decades were compared. A total of 2148 patients underwent CRS and HIPEC, of which 78% had CCR. Gastrectomy was performed in 7.1%. Median age was 55 years, and 52% were female. Among gastrectomy patients, 94.2% had ≥1 elevated tumour marker, and 18% had high-grade disease. Median PCI was 30, and 30% required subtotal colectomy. Clavien-Dindo III-IV complications occurred in 32%, and 90-day mortality was 1.75%. Median survival was 104 months, and 10-year OS was 47%. Comparing the two decades, total CRS cases almost tripled, with a greater proportion achieving CCR (82.2% vs. 67.8%) but fewer requiring gastrectomy (5.3% vs. 13.5%). In those who had gastrectomy, disease was more advanced (higher PCI, more high-grade disease, more colectomies) in the later period. However, on multivariable analysis, there was no difference in survival between decades. High-grade histology was the only predictor of survival. Gastrectomy can achieve good long-term survival with low mortality and acceptable morbidity and should not deter surgeons from achieving CCR. However, increasing experience shows CCR can be achieved, preserving the stomach in the majority of cases through careful consideration of the anatomy and gastric blood supply.

A 10-year retrospective study of the risks and peculiarities in pediatric patients with (para)gonadal tumors and cysts.

Gonadal pediatric tumors are rare, ranking fourth (6%) among pediatric tumors, by Surveillance, Epidemiology, and End Results Program (https:∕∕seer.cancer.gov∕). They have vague symptoms, leading to late discovery, but early detection and identifying its risk factors result in favorable prognosis and reduction of its incidence respectively. A 10-year retrospective study identified peculiarities and risk factors in 210 children till age 17 with (para)gonadal tumors. Stress, pollution (agricultural chemicals, insecticides and metal mine), obesity, breastfeeding ≤5 months, malformations [mainly non-genetic related 67∕87 (77%), especially eye malformation - 64%], hormone, smoking, positive heredo-genetic history, rural residence area, abnormal birth weight, and menstruation disorders showed an increased gonadal malignancy risk; relative risk ratio (RR): 1.33, 1.30, 1.34, 1.11, 1.65, 1.16, 1.36, 1.10, 1.00, 1.08 and 1.15 folds, respectively. RR for histopathological subtypes: immature teratoma (IT) (pollution - 1.75, Rhesus positive - 3.41), dysgerminoma (menstruation disorders - 2.80), granulosa cell tumor (stress - 2.10, menstruation disorders - 2.80), mucinous cystadenomas (obesity - 2.84, no postnatal vaccine - 3.71), mature teratomas (stress - 2.35, malformations - 2.18) and serous cystadenomas (breastfeeding ≤5 months - 2.53), dependent variables being mixed germ cell tumors (GCTs) and cysts. Children presenting with bleeding (73%), abdominal distention (62%), elevated tumor markers (91%), (multilocular) solid tumor (88% and 100%), tumor size >10 cm (65%), GCTs (74%), death (100%), metastases (100%), viruses (77%), loss of appetite (68%), and weight (85%), had gonadal malignant tumors, especially mixed GCTs and IT. Avoiding these risk factors will prevent and reduce gonadal pediatric tumors. Investigating children presenting with the listed peculiarities, especially if exposed to the mentioned risk factors, will enable early gonadal tumor identification, successful patient management, and favorable prognosis.

Hepatopancreatoduodenectomy with delayed division of the pancreatic parenchyma when utilizing a right lateral approach to the superior mesenteric artery

BackgroundHepatopancreatoduodenectomy (HPD) is a high-risk surgical procedure. Delayed division of the pancreatic parenchyma (DDPP) was reported as a novel technique in HPD for reducing postoperative pancreatic fistula. However, it is often difficult to dissect the pancreatic head nerve plexus while leaving the pancreatic parenchyma intact, particularly in patients with a bulky tumor with vascular invasion. Of the various reported approaches to the superior mesenteric artery, the right lateral approach can provide a useful surgical field to conduct DDPP in HPD.Case presentationA 78-year-old man visited a local clinic with itching and jaundice. Laboratory tests revealed elevated hepatobiliary enzyme, total bilirubin, and tumor markers. Enhanced computed tomography, endoscopic retrograde cholangiopancreatography, and intraductal ultrasonography of the bile duct were performed, and he was diagnosed with perihilar cholangiocarcinoma with invasion to the right hepatic artery (40 × 15 mm, Bismuth IIIa, cT3N0M0 cStage III). After neoadjuvant chemotherapy, he underwent left hepatectomy with caudate lobectomy, pancreatoduodenectomy, and combined resection of right hepatic artery using DDPP with a right lateral approach to the superior mesenteric artery. The pathological diagnosis was perihilar cholangiocarcinoma ypT3N1M0 ypStage IIIC, R0 resection. He was discharged on postoperative day 57 in good health and has been doing well for 6 months since the surgery.ConclusionsWe present an effective application of the right lateral approach to the superior mesenteric artery in DDPP during HPD. This procedure can provide a clear surgical field to easily divide the pancreatic head nerve plexus before transection of the pancreatic parenchyma.

Elevated Serum Tumor Markers (HE4 and ROMA Score) and Increased Treg Cells Distinguished Ovarian Cancer and Benign Tumor

BACKGROUND: Tumor markers such as human epididymis protein 4 (HE4), cancer antigen 125 (CA-125), and risk of ovarian malignancy algorithm (ROMA) are frequently utilized for diagnostic and prognostic purposes. Lymphocytes, essential immune cells, play a significant role in eliminating cancer cells. However, the precise correlation between tumor markers and lymphocytes remains incompletely elucidated. The aim of this study was to explore the correlation between tumor markers and lymphocyte subtype profiles in differentiating ovarian cancer and benign tumors.METHODS: This was a cross-sectional study involving 12 ovarian cancer and 17 benign ovarian tumor patients. Blood samples were collected for the characterization of T lymphocytes, B lymphocytes, natural killer (NK), and T regulatory (Treg), which were analyzed using flowcytometry. Additionally, tumor markers HE4 and CA-125 were measured from patient serum using the chemiluminescent microparticle immunoassay (CMIA) method.RESULTS: Benign ovarian tumors and ovarian cancer can be distinguished by a significant increase in HE4 levels (p=0.004), ROMA (p=0.004), and Treg cells (CD4+/CD25+/FOXP3+, p=0.017). Furthermore, the correlation between tumor markers and lymphocytes indicates that an increase in ROMA was weakly correlated with an increase in the percentage of T regulatory cells (CD4+/CD25+/FOXP3+, r=0.553, p=0.006) and B lymphocytes (CD19+, r=0.528, p=0.010), accompanied by a decrease in the number of T lymphocytes (CD3+, r=-0.598, p=0.003), T helper lymphocytes (CD3+CD4+, r=-0.594, p=0.003), and cytotoxic lymphocytes (CD3+CD8+, r=-0.510, p=0.013).CONCLUSION: The elevation of serum tumor markers (HE4 and ROMA) accompanied by an increase in Treg cells can distinguish between benign ovarian tumor patients and ovarian cancer patients.KEYWORDS: tumor marker, CA-125, HE4, ROMA, subtype of lymphocytes, ovarian cancer

Gastrointestinal Stromal Tumors (GISTs) Mimicking Primary Ovarian Tumors or Metastasizing to the Ovaries: A Systematic Literature Review.

Background: Gastrointestinal stromal tumors (GISTs) are a rare neoplasm, sometimes mimicking primary ovarian tumors (OTs) and/or metastasizing to the ovaries (M-OT). We performed a systematic literature review (SLR) of OTs and M-OTs, investigating differences in recurrence-free and overall survival. Methods: Our SLR was performed according to PRISMA guidelines, searching in Pubmed, Scopus, and Web of Science databases from inception until 21 April 2024. Results: Overall, 59 OTs (Group 1) and 21 M-OTs (Group 2) were retrieved. The absence of residual disease after surgery was achieved significantly in a higher percentage of patients with Group 1 GISTs (91.5%) compared with Group 2 GISTs (57.1%). Chemotherapy was more frequently administered to Group 2 patients (33% vs. 0%). Recurrence and deaths for disease were significantly more frequent in Group 2 than Group 1 cases (54.5% vs. 6.8%, and 37.5% vs. 9.8%, respectively). Conclusions: GISTs can rarely mimic primary ovarian cancers or even more rarely metastasize to the ovaries. Group 1 GISTs occurred in younger women, were not associated with elevated tumor markers, and had a better prognosis. In contrast, Group 2 GISTs occurred in older women, may exhibit elevated tumor markers, and presented a worse prognosis. However, no significant statistical difference for survival between the two studied groups was detected. Computed tomography scans can define the size of GISTs, which correlate to stage and prognostic risk classes. The gold standard treatment is complete surgical resection, which was achieved in almost all cases of Group 1 GISTs and in half of Group 2. Histopathology and immunohistochemistry are essential for the final diagnosis and guide chemotherapy treatment.

Diagnostic Performance of F-18 FDG PET/CT in the Detection of Recurrent Colorectal Cancer: Correlation with Biochemical Markers and Conventional Imaging Modalities.

Background/Objectives: Although the role of PET/CT imaging is well established in oncology, its diagnostic value in routine monitoring for recurrent colorectal cancer (CRC) is still controversial. The aim was to evaluate the diagnostic value of F-18 FDG PET/CT in detecting recurrent CRC in correlation with CEA, CA 19-9 levels, and conventional imaging modalities (CIM). Methods: Between 2009 and 2023, a retrospective study was performed including 134 CRC patients referred for PET/CT imaging on the suspicion of recurrence, based on elevated CEA and/or CA 19-9 and/or equivocal CIM findings. According to our institution's Tumor Board CRC protocol, after the initial treatment, which was dependent on the TNM stage (neoadjuvant therapy, primary resection, or adjuvant treatment), patients underwent a standard 5-year surveillance including CEA and CA 19-9 measurements, CIM, and colonoscopy, every six months. The statistics, including univariate and multivariate analyses were conducted using the IBM SPSS 20.0 statistical software. p-values < 0.05 were considered statistically significant. Results: Recurrent CRC was confirmed in 54/134 (40.3%) patients with elevated tumor markers. PET/CT showed high diagnostic performance in detecting recurrent CRC with sensitivity, specificity, PPV, NPV, and accuracy of 94.4%, 82.5%, 78.5%, 95.7%, and 87.3%, respectively. The CEA showed a high sensitivity of 98.1% but both low specificity and accuracy of 15% and 48.5%, respectively. The sensitivity, specificity, and accuracy for CA 19-9 and CIM for diagnosis of CRC recurrence were 44.4%, 67.5%, 58.2%, and 51.9%, 98.8%, 79.9%, respectively. The AUC for PET/CT, elevated CEA levels, CIM, and elevated CA 19-9 levels was 0.885 (95% CI: 0.824-0.946; p < 0.001), 0.844 (95% CI: 0.772-0.916; p < 0.001), 0.753 (95% CI: 0.612-0.844; p < 0.001), and 0.547 (95% CI: 0.442-0.652; p = 0.358), respectively. Univariate analysis showed that both PET/CT and CIM positive results were highly associated with CRC recurrence (p < 0.001 and p < 0.001, respectively). At the same time, gender, mucinous tumor type, presence of initial lymph node metastasis (N+), and presence of initial distant metastasis (M+) had no significance (p = 0.211, p = 0.158, p = 0.583, and p = 0.201, respectively). Our multivariate analysis showed that independent predictors for CRC recurrence are positive PET/CT scans (p < 0.001), positive CIM results (p = 0.001), and elevated CA 19-9 levels (p = 0.023). Although CA 19-9 was not detected as a statistically significant predictor in the univariate analysis (p = 0.358), in a multivariate analysis it was recognized as a significant predicting factor in detecting the CRC recurrence (p = 0.023). Conclusions: F-18 FDG PET/CT showed high diagnostic efficacy in CRC recurrence detection, in correlation with CEA levels, CA 19-9 levels, and CIM. This imaging modality should be routinely integrated into the post-operative follow-op in patients with elevated tumor markers.

Role of transarterial chemoembolization for hepatocellular carcinoma with extrahepatic metastases in the era of advancing systemic therapy.

Systemic therapy is the current standard treatment for hepatocellular carcinoma (HCC) with extrahepatic metastasis (EHM). However, some patients with HCC and EHM undergo transarterial chemoembolization (TACE) to manage intrahepatic tumors. Herein, we aimed to explore the appropriateness of TACE in patients with HCC and EHM in an era of advanced systemic therapy. This study analyzed 248 consecutive patients with HCC and EHM (median age, 58.5 years; male, 83.5%; Child-Pugh A, 88.7%) who received TACE or systemic therapy (83 sorafenib, 49 lenvatinib, 28 immunotherapy-based) between January 2018 and January 2021. Among the patients, 196 deaths were recorded during a median follow-up of 8.9 months. Patients who received systemic therapy had a higher albumin-bilirubin grade, elevated tumor markers, an increased number of intrahepatic tumors, larger-sized tumors, and more frequent portal vein invasion than those who underwent TACE. TACE was associated with longer median overall survival (OS) than sorafenib (15.1 vs. 4.7 months; 95% confidence interval [CI], 11.1-22.2 vs. 3.7-7.3; hazard ratio [HR], 1.97; P<0.001). After adjustment for potential confounders, TACE was associated with statistically similar survival outcomes to those of lenvatinib (median OS, 8.0 months; 95% CI, 6.5-11.0; HR, 1.21; P=0.411) and immunotherapies (median OS, 14.3 months; 95% CI, 9.5-27.0; HR, 1.01; P=0.973), demonstrating survival benefits equivalent to these treatments. In patients with HCC and EHM, TACE can provide a survival benefit comparable to that of newer systemic therapies. Accordingly, TACE remains a valuable option in this era of new systemic therapies.

Emergency treatment for primary intracranial germ cell tumours (PICGCTs).

e17020 Background: PICGCTs arise de novo in children and young adults, most frequently in the pineal or suprasellar regions. Here, we evaluate the acute pathway for patients (pts) with PICGCTs managed at our Emergency Cancer Treatment Centre. Methods: Retrospective observational study from 1984-2022 at a single institution. Data was collected from paper and electronic patient records for all PICGCT pts, including pts treated with our intracranial regimen EP-OMB (Etoposide-Cisplatin alternating every week with Vincristine-Methotrexate-Bleomycin) administered with and without intrathecal Methotrexate. Results: To date, we have identified 43 pts with intracranial disease treated at our Centre over 38 years: 25 pts (58%) with PICGCT, 18pts (42%) with germ cell tumour brain metastases treated with EP-OMB and excluded from analysis. Most PICGCT pts are male (92%, n=23) with a median age 25 (range 17-50). The majority present with symptomatic disease (88%, n=22) confined to the pineal gland (72%, n=18), with hormone dysfunction in 24% ( n=6). Only two female pts (8%) have presented with suprasellar and pituitary midline lesions causing headache, progressive visual loss and hypothalamic failure including cranial diabetes insipidus. Eloquent areas in the brain cannot be biopsied so only 60% PICGCTs ( n=15) were confirmed histologically, 47% as germinoma ( n=7), 27% dysgerminoma ( n=4), 27% unclassified ( n=4). Tumour markers (TM) were elevated in all pts with cerebrospinal fluid (CSF) evaluation ( n=5) compared to elevated serum TM in under half (44%, n=12). 68% pts required emergency treatment for a new cancer diagnosis ( n=17): neurosurgery (59%, n=10), chemotherapy (35%, n=6) or radiotherapy (6%, n=1). 88% PICGCT pts received EP-OMB ( n=22) with intrathecal Methotrexate in 63% ( n=14). For all PICGCT pts, 72% pts remain alive ( n=18) with median follow-up 3.8 years (range 0.2-27.3). For 36% pts with TM relapse or radiological progression despite treatment ( n=9), 44.4% remain alive ( n=4) with median overall survival at 6.8 years (range 1.1-18.6). Conclusions: PICGCT pts frequently require emergency surgical treatment for a new cancer diagnosis. Although rare, accurate diagnosis will affect management and prognosis in this young patient group. CSF rather than serum TM analysis is crucial for diagnostic work-up. Consensus on optimal management is warranted given the potential toxicity from multiple therapeutic interventions administered with curative intent.

Study on the efficacy and toxicity of pamiparib combined with tamoxifen in the treatment of patients with epithelial ovarian cancer with biochemical recurrence during first-line PARPi maintenance therapy.

TPS5621 Background: A high proportion of ovarian cancer patients tend to have elevated CA-125 1-6 months before imaging recurrence. The time between biochemical recurrence (i.e., only elevated CA-125 without imaging finding or clinical symptoms) to imaging recurrence can be considered a "window period", and if the “window period” can be extended, it may convert platinum-resistant relapsed patients to platinum-sensitive patients, and ultimately improving patient outcomes. The timing of treatment for the biochemical recurrent patients has been controversial. Tamoxifen, an anti-estrogenic drug, is considered an effective option for these patients. Pamiparib (BGB-290) is an investigational small molecule inhibitor of PARP1 and PARP2. According to OReO study(NCT03106987), the "PARPi after PARPi" strategy is effective in recurrent ovarian cancer patients previously treated with a PARP inhibitor. Therefore, we aim to further explore the use of PARP inhibitors in maintenance therapy for patients with ovarian cancer. Methods: This study (NCT05669768) will evaluate the efficacy and toxicity of pamiparib and tamoxifen in ovarian cancer patients with biochemical recurrence during first-line PARPi maintenance therapy. The included ovarian cancer patients are required to achieve No Evidence of Disease (NED) or demonstrated a response following platinum-based chemotherapy, with normalized CA-125 levels. First-line maintenance treatment with a PARP inhibitor is mandatory, with a minimum interval of ≥6 months to biochemical recurrence. The trial design is interventional, employing a Simon two-stage design to estimate sample size. The primary outcome of the study is the CA-125 response rate, which was assessed according to the GCIG criteria.1 The secondary outcome was Time to First Subsequent Therapy (TFST). Patients undergo regular assessments for tumor markers and imaging throughout treatment. If persistent elevation of tumor markers or the detection of recurrent lesions or distant metastases is observed, the patient is promptly removed from the study group. Standardized antitumor therapy is then initiated based on the patient's condition. The total planned enrollment is 46 participants, utilizing a single-group assignment and an open-label design. 1 of planned 12 patients for the first stage of accrual have been enrolled. Reference: 1. Rustin GJ, Vergote I, Eisenhauer E, et al. Definitions for response and progression in ovarian cancer clinical trials incorporating RECIST 1.1 and CA 125 agreed by the Gynecological Cancer Intergroup (GCIG). Int J Gynecol Cancer. 2011;21(2):419-423. Clinical trial information: NCT05669768 .

Prognostic Significance of Preoperative and Postoperative Evaluation of Combined Tumor Markers for Patients With Colon Cancer.

The combined value of the tumor markers carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) in patients with colon cancer (CC) is unclear. This study aimed to investigate the role of composite tumor markers in the prognosis of CC. Patients who underwent curative resection of colon adenocarcinoma were enrolled. The tumor marker status before and after the operation was used to divide the patients into groups according to the number of tumor markers with abnormal expression, and recurrence-free survival (RFS) and overall survival (OS) of different groups were compared. The impact of changes in composite tumor markers in the perioperative period on outcomes was further explored. Ultimately, 531 patients were enrolled in the study. As the number of preoperative and postoperative elevated tumor markers increased, both RFS and OS rates became lower (both P <0.05). Further analysis revealed that the number of elevated tumor markers after resection can significantly affect the outcomes (both P <0.05). In patients with abnormal preoperative tumor markers, normalization of markers after surgery was a protective factor for prognosis (both P <0.05), and patients with postoperative elevated levels of both tumor markers had a 5.5-fold and 6-fold increase in the risk of recurrence and death. In addition, patients with elevated markers after surgery had a high risk of recurrence within 5 years after colectomy. Postoperative tumor markers had a better ability to differentiate postoperative outcomes in patients with CC than preoperative tumor markers. Patients whose tumor markers normalized after surgery had a better prognosis.

Prognostic Value of Preoperative MRI-derived 3D Quantitative Tumor Arterial Burden in Patients with Hepatocellular Carcinoma Receiving Transarterial Chemoembolization.

Purpose To investigate the association of tumor arterial burden (TAB) on preoperative MRI with transarterial chemoembolization refractoriness (TACER) and progression-free survival (PFS) in patients with hepatocellular carcinoma (HCC). Materials and Methods This retrospective study included patients with HCC who underwent repeated transarterial chemoembolization (TACE) treatments between January 2013 and December 2020. HCC was confirmed with pathology or imaging, and patients with other tumors, lost follow-up, or with a combination of other treatments were excluded. TACER was defined as viable lesions of more than 50% or increase in tumor number after two or more consecutive TACE treatments, continuous elevation of tumor markers, extrahepatic spread, or vascular invasion. TAB assessed with preoperative MRI was divided into high and low groups according to the median. A Cox proportional hazards model was used to determine the predictors of TACER and PFS. Results A total of 355 patients (median age, 61 years [IQR, 54-67]; 306 [86.2%] men, 49 [13.8%] women) were included. During a median follow-up of 32.7 months, the high TAB group had significantly faster TACER and decreased PFS than the low TAB group (all log-rank P < .001). High TAB was the strongest independent predictor of TACER and PFS in multivariable Cox regression analyses (hazard ratio [HR], 2.23 [95% CI: 1.51, 3.29]; HR, 2.30 [95% CI: 1.61, 3.27], respectively), especially in patients with Barcelona Clinic Liver Cancer stage A or a single tumor. The restricted cubic spline plot demonstrated that the HR of TACER and PFS continuously increased with increasing TAB. Conclusion High preoperative TAB at MRI was a risk factor for faster refractoriness and progression in patients with HCC treated with TACE. Keywords: Interventional-Vascular, MR Angiography, Hepatocellular Carcinoma, Transarterial Chemoembolization, Progression-free Survival, MRI Supplemental material is available for this article. © RSNA, 2024.

The application of different machine learning models based on PET/CT images and EGFR in predicting brain metastasis of adenocarcinoma of the lung

ObjectiveTo explore the value of six machine learning models based on PET/CT radiomics combined with EGFR in predicting brain metastases of lung adenocarcinoma.MethodsRetrospectively collected 204 patients with lung adenocarcinoma who underwent PET/CT examination and EGFR gene detection before treatment from Cancer Hospital Affiliated to Shandong First Medical University in 2020. Using univariate analysis and multivariate logistic regression analysis to find the independent risk factors for brain metastasis. Based on PET/CT imaging combined with EGFR and PET metabolic indexes, established six machine learning models to predict brain metastases of lung adenocarcinoma. Finally, using ten-fold cross-validation to evaluate the predictive effectiveness.ResultsIn univariate analysis, patients with N2-3, EGFR mutation-positive, LYM%≤20, and elevated tumor markers(P<0.05) were more likely to develop brain metastases. In multivariate Logistic regression analysis, PET metabolic indices revealed that SUVmax, SUVpeak, Volume, and TLG were risk factors for lung adenocarcinoma brain metastasis(P<0.05). The SVM model was the most efficient predictor of brain metastasis with an AUC of 0.82 (PET/CT group),0.70 (CT group),0.76 (PET group).ConclusionsRadiomics combined with EGFR machine learning model as a new method have higher accuracy than EGFR mutation alone. SVM model is the most effective method for predicting brain metastases of lung adenocarcinoma, and the prediction efficiency of PET/CT group is better than PET group and CT group.

Serum Tumor Markers and Outcomes in Patients With Appendiceal Adenocarcinoma

Serum tumor markers carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), and cancer antigen 125 (CA125) have been useful in the management of gastrointestinal and gynecological cancers; however, there is limited information regarding their utility in patients with appendiceal adenocarcinoma. To assess the association of serum tumor markers (CEA, CA19-9, and CA125) with clinical outcomes and pathologic and molecular features in patients with appendiceal adenocarcinoma. This is a retrospective cohort study at a single tertiary care comprehensive cancer center. The median (IQR) follow-up time was 52 (21-101) months. Software was used to query the MD Anderson internal patient database to identify patients with a diagnosis of appendiceal adenocarcinoma and at least 1 tumor marker measured at MD Anderson between March 2016 and May 2023. Data were analyzed from January to December 2023. Association of serum tumor markers with survival in patients with appendiceal adenocarcinoma. Cox proportional hazards regression analyses were also performed to assess associations between clinical factors (serum tumor marker levels, demographics, and patient and disease characteristics) and patient outcomes (overall survival). A total of 1338 patients with appendiceal adenocarcinoma were included, with a median (range) age at diagnosis of 56.5 (22.3-89.6) years. The majority of the patients had metastatic disease (1080 patients [80.7%]). CEA was elevated in 742 of the patients tested (56%), while CA19-9 and CA125 were elevated in 381 patients (34%) and 312 patients (27%), respectively. Individually, elevation of CEA, CA19-9, or CA125 were associated with worse 5-year survival; elevated vs normal was 81% vs 95% for CEA (hazard ratio [HR], 4.0; 95% CI, 2.9-5.6), 84% vs 92% for CA19-9 (HR, 2.2; 95% CI, 1.4-3.4), and 69% vs 93% for CA125 (HR, 4.6; 95% CI, 2.7-7.8) (P < .001 for all). Quantitative evaluation of tumor markers was associated with outcomes. Patients with highly elevated (top 10th percentile) CEA, CA19-9, or CA125 had markedly worse survival, with 5-year survival rates of 59% for CEA (HR, 9.8; 95% CI, 5.3-18.0), 64% for CA19-9 (HR, 6.0; 95% CI, 3.0-11.7), and 57% for CA125 (HR, 7.6; 95% CI, 3.5-16.5) (P < .001 for all). Although metastatic tumors had higher levels of all tumor markers, when restricting survival analysis to 1080 patients with metastatic disease, elevated CEA, CA19-9, or CA125 were all still associated worse survival (HR for CEA, 3.4; 95% CI, 2.5-4.8; P < .001; HR for CA19-9, 1.8; 95% CI, 1.2-2.7; P = .002; and HR for CA125, 3.9; 95% CI, 2.4-6.4; P < .001). Interestingly, tumor grade was not associated with CEA or CA19-9 level, while CA-125 was slightly higher in high-grade tumors relative to low-grade tumors (mean value, 18.3 vs 15.0; difference, 3.3; 95% CI, 0.9-3.7; P < .001). Multivariable analysis identified an incremental increase in the risk of death with an increase in the number of elevated tumor markers, with an 11-fold increased risk of death in patients with all 3 tumor markers elevated relative to those with none elevated. Somatic mutations in KRAS and GNAS were associated with significantly higher levels of CEA and CA19-9. In this retrospective study of serum tumor markers in patients with appendiceal adenocarcinoma, CEA, CA19-9, and CA125 were associated with overall survival in appendiceal adenocarcinoma. Given their value, all 3 biomarkers should be included in the initial workup of patients with a diagnosis of appendiceal adenocarcinoma.

Semen parameters in testicular tumor patients before orchiectomy: What is the impact of testicular tumor stage and histology?

To evaluate the influence of testicular cancer histology and stage on sperm parameters in cryopreserved samples collected prior to orchiectomy. We conducted a retrospective analysis of tumor histology, stage and sperm parameters of patients who underwent pre-orchiectomy sperm cryopreservation for testicular cancer between March 2010 and March 2023. The World Health Organization (WHO) 2010 sperm reference values were used to identify patients with subnormal semen parameters and to further categorize patients by sperm alteration. Localized disease was classified as Stage I, while metastatic disease encompassed Stages II and III. Continuous variables were compared using t-test or Mann Whitney U test, and categorical variables using Chi-square and Fisher´s exact test. A total of 64 patients was identified, 48 (75%) classified as stage I and 16 (25%) classified as stage II/III. No difference was found in semen parameters between patients with seminoma and patients with non-seminoma germ cell tumor (NSGCT). Patients with stage II/III disease had significantly lower percentages of progressive motility (36% vs 53%, p = 0.021) and total motility (60% vs 69%, p = 0.015) than stage I patients. When categorizing by sperm alterations according to WHO 2010 reference values, patients with stage II/III disease had significantly higher proportions of asthenozoospermia (38% vs 15%, p = 0.048) and teratozoospermia (63% vs 31%, p = 0.027) than stage I patients. Elevated tumor markers were not associated with sperm abnormalities. Patients with metastatic testicular cancer present with worse sperm quality than patients with localized disease. Sperm cryopreservation should be offered to all patients with testicular cancer, and especially emphasized in patients with metastatic disease.

EHMT2/G9a and EZH2: Epimarkers in testicular germ cell tumors.

Testicular germ cell tumors remain the most frequent solid malignancies in young males. Despite excellent prognosis, the fact that only 60% of patients at diagnosis have elevated serum tumor markers (dependent on stage and histology) and the poor quality of life of patients who develop resistance to chemotherapy cannot be neglected. Consequently, it is mandatory to bring out novel biomarkers. The main goal was to evaluate EZH2 and EHMT2/G9a immunoexpression in a well-characterized patients' cohort of primary and metastatic testicular germ cell tumors, seeking associations with clinicopathological features and discovering differential immunoexpression patterns among specific subtypes. First, an in silico analysis of the Cancer Genome Atlas database was performed regarding EZH2 and EHMT2/G9a. Then, immunohistochemistry for EZH2 and EHMT2/G9a was carried out in a cohort of testicular germ cell tumor patients, comprising 155 chemo-naïve primary tumors and 11 chemo-treated metastases. Immunoexpression was evaluated using a digital pathology analysis software. Higher EZH2 and EHMT2/G9a expression levels were found in non-seminoma in the in silico analysis, particularly in embryonal carcinoma. Through digital pathology analysis, non-seminomas showed significantly higher EZH2 and EHMT2/G9a immunoexpression, with embryonal carcinoma showing higher expression. Moreover, mixed tumors with 50% or more of embryonal carcinoma component revealed the highest nuclei positivity for both biomarkers. Cisplatin-exposed metastases demonstrated a higher EZH2-positive nuclei and H-score, as well as higher EHMT2/G9a-positive nuclei. Overall, our data suggest that EZH2 and EHMT2/G9a might be associated with greater aggressiveness and, eventually, involved in the metastatic setting, paving the way for testing targeted therapies.

Attitudes and health behaviors of middle-aged and older adults with elevated tumor markers in China.

To understand the attitudes and health behaviors of middle-aged and older adults in China after receiving elevated results of tumor markers (TMs) test in the annual health examinations (AHEs) and explore the influencing factors. A three-section online questionnaire survey was conducted from March 1 to April 30, 2020 in Hangzhou, China, to people who were aged 45 and older and had at least one elevated result of TMs test. Clinical information was collected from the online survey and medical records. Descriptive statistics were carried out followed by regression analyses. Of 380 participants, 76.1% were unwilling to quit the TMs test in AHEs, whereas 75.3% would take the doctor's advice and quit unnecessary TMs test; 67.4% felt stressed about their TMs. Among participants with elevated TMs, 76.8% changed lifestyle to keep healthy, 74.2% sought health information, 58.9% requested a TMs retest, and 50.3% did further tests to confirm a diagnosis. Family history of cancer was associated with lifestyle changing; education level, area of residence and health insurance were associated with health information seeking; comorbidity were associated with retests and sequential confirming tests. The application of the TMs test in AHEs among Chinese people may lead to positive and negative behavioral consequences and psychological distress. Doctors have a significant impact on patients' health behaviors. Accurate indications and adequate communication with patients before and after the TMs test are in great need.