Initial Diagnosis Of Recurrence Research Articles

Systemic Treatment of Recurrent Hepatocellular Carcinoma after Liver Transplantation: A Multicenter Trial.

The tyrosine kinase inhibitors (TKIs) sorafenib and lenvatinib represent the first-line systemic therapy of choice for patients with hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT). Under sorafenib and lenvatinib, HCC patients have shown increasingly improved overall survival in clinical studies over the years. In contrast, data on overall survival for patients with HCC recurrence after LT under TKIs are scarce and limited to small retrospective series. In this retrospective, multicenter study, we investigated the efficacy of TKI therapy and the influence of immunosuppression in patients with HCC recurrence after LT. Retrospective data were collected from four transplant centers from Germany and Austria. We included patients with HCC recurrence after LT between 2007 and 2020 who were treated with a TKI. In total, we analyzed data from 46 patients with HCC recurrence after LT. The most common underlying liver disease was hepatitis C, accounting for 52.2%. The median time to relapse was 11.8 months (range 0-117.7 months). The liver graft was affected in 21 patients (45.7%), and 36 patients (78.3%) had extrahepatic metastases at initial diagnosis of recurrence, with the lung being the most commonly affected (n = 25, 54.3%). Of the total, 54.3% (n = 25) of the patients were initially treated locally; 39 (85.8%) and 7 (15.2%) patients received sorafenib and lenvatinib, respectively, as first-line systemic therapy. Median overall survival of the whole cohort was 10.9 months (95% confidence interval (95% CI) 6.9-14.9 months) and median progression free survival was 5.7 months (95% CI 2.0-9.4 months) from treatment initiation. Since history of liver transplantation is considered a contraindication for immunotherapy, prognosis of patients with HCC recurrence after LT remains poor.

CLRM-04. PHASE I/II SAFETY AND EFFICACY STUDY OF BET BROMODOMAIN INHIBITOR OTX-015 WITH OLAPARIB AND LOMUSTINE IN PATIENTS WITH RECURRENT GLIOBLASTOMA

Standard of care for patients with glioblastoma (GBM) includes resection with concurrent temozolomide (TMZ) and radiotherapy, with inevitable disease recurrence. Upon recurrence, tumors are often resistant to first-line therapies and/or have infiltrated eloquent or deep brain regions, precluding repeat resection. There is currently no standard of care for recurrent GBM and patients succumb to their disease burden within 12- 15 months of their initial diagnosis of recurrence, exposing an unmet need to find novel therapies to treat recurrent disease. Bromodomain and extraterminal (BET) proteins are chromatin readers that affect transcription of genes. The oral BET inhibitor (BETi) OTX-015 has shown promise in a dose-escalation, phase I study in patients with acute leukemia and other BET inhibitors are currently in phase I studies for the treatment of primary brain tumors. We have recently shown that BET inhibition increases DNA damage and mitotic catastrophe in oncogenic cells by increasing transcription-replication conflicts and downregulating expression of key DNA damage checkpoint proteins, and have also shown its efficacy in decreasing tumor burden and improving survival when combined with TMZ in intracranial mouse models of glioma. We have also demonstrated that BETi's synergize with Olaparib by downregulating expression of the BRCA-driven DNA damage repair pathway and further leverages additive effects when triply combined with other DNA damaging agents such as Lomustine to decrease tumor burden and improve survival in patient-derived mouse models of GBM and medulloblastoma. We therefore hypothesize that the synergistic and additive effects of this triple combination seen in our preclinical studies will achieve therapeutic benefits in patients with recurrent GBM.

Association of CA 15-3 and CEA with Clinicopathological Parameters In Patients With Metastatic Breast Cancer

Background. Breast cancer is the most common cancer and the leading cause of cancer death for women, a third of women are diagnosed with breast cancer at a late stage when the disease has a poor prognosis. Serum tumor markers have been widely used as noninvasive tools for measuring treatment response, early diagnosis of recurrence and predicting prognosis. In breast cancer, the most widely used serum tumor markers are cancer antigen 15-3 (CA 15-3) and carcinoembryonic antigen (CEA). The aim of this study was to investigate the association of serum CA15-3 and CEA levels with clinicopathological parameters in patients diagnosed with metastatic breast cancer (MBC). Patients and methods. This retrospective study was conducted on 50 patients who had used to predict response to chemotherapy in patients with metastatic breast cancer. The concentration of serum CA15-3 and CEA levels were measured using chemiluminescent enzyme immunoassays (ABBOTT ARCHITECT). The upper limits of normal for CA15-3 and CEA were 31.3 U/ml and 5 ng/ml, respectively. Result. Of the 50 patients, elevated CA 15-3 and CEA levels at initial diagnosis of recurrence were identified in 37 (74%) and 32 (64%) patients, respectively. Elevated CA 15-3 and CEA levels were significantly associated with breast cancer molecular subtypes (P=0.005 and P=0.008, respectively). Elevated CA 15-3 level was correlated with bone metastasis (P=0.047). Conclusion. CA 15-3 and CEA level elevation at initial diagnosis of recurrence were found to be associated with breast cancer molecular subtype; these serum tumor markers are frequently increased in the HER2-enriched and triple negative (TN) molecular subtypes of breast cancer.

ACE et diagnostic précoce de récidive dans les différents sous-types moléculaires de cancer du sein : comparaison au CA 15-3

This retrospective study evaluates the interest of CEA measurement for early detection of breast cancer recurrences. Among 804patients with invasive breast cancer, we selected 97patients without recurrence (WR) for 5years or more, 32with a local recurrence (LR) and 131with at least one distant metastasis (DM). Elevated CEA and CA15-3levels (>3.1μg/L and >26kU/L respectively) were found in 6% and 22% of patients with RL respectively and in 49% and 69% of patients with DM. Both CEA and CA15-3retained a significant value in predicting DM by univariate and multivariate analysis. Higher sensitivity of CEA and CA15-3were found in tumors with positive hormonal receptor status. CEA and CA15-3levels at DM were raised respectively in 23and 65% of the triple negative group, 58and 75% of the luminal, 56and 78% of the luminal-HER2and 50and 30% of HER2-enriched group (P=0.0094and 0.0252respectively). The combination of CEA and CA15-3increased CA15-3sensitivity in especially luminal and HER2-enriched groups. In conclusion, elevated CA15-3and CEA levels at initial diagnosis of recurrence were found to be associated with hormonal receptor status and breast cancer subtypes. The combination of CEA and CA15-3appeared useful especially luminal and HER2-enriched groups.

Association of CA 15-3 and CEA with clinicopathological parameters in patients with metastatic breast cancer.

The objective of this study was to investigate the association of serum cancer antigen 15-3 (CA 15-3) and carcinoembryonic antigen (CEA) levels with clinicopathological parameters in patients diagnosed with metastatic breast cancer (MBC). We retrospectively evaluated the medical records of 284 patients diagnosed with MBC between January, 2007 and December, 2012 who fulfilled the specified criteria and the association between the levels of the two tumor marker and clinicopathological parameters was analyzed. Of the 284 patients, elevated CA 15-3 and CEA levels at initial diagnosis of recurrence were identified in 163 (57.4%) and 97 (34.2%) patients, respectively. Elevated CA 15-3 and CEA levels were significantly associated with breast cancer molecular subtypes (P<0.001 and P=0.032, respectively). Cases with luminal subtypes exhibited a higher percentage of elevated CA 15-3 and CEA levels compared to non-luminal subtypes. Elevated CA 15-3 level was correlated with bone metastasis (P=0.017). However, elevation of CEA was observed regardless of the site of metastasis. Elevation of CA 15-3 was significantly more common in MBC with multiple metastatic sites compared to MBC with a single metastasis (P=0.001). However, the incidence of elevated CEA levels did not differ between patients with a single and those with multiple metastatic sites. In conclusion, elevated CA 15-3 and CEA levels at initial diagnosis of recurrence were found to be associated with breast cancer molecular subtypes, whereas an elevated CA 15-3 level was significantly correlated with bone metastasis and an elevated CEA level was observed regardless of metastatic site. The proportion of MBC cases with elevated CA 15-3 levels differed according to the number of metastatic sites.

Parietal Bone Metastasis of Rectal Adenocarcinoma as an Initial Diagnosis of Recurrence: Case Report

Parietal Bone Metastasis of Rectal Adenocarcinoma as an Initial Diagnosis of Recurrence: Case Report

Clinical characteristics and treatment outcomes of gastric cancer patients with isolated para-aortic lymph node involvement

Although gastric cancer with isolated para-aortic lymph node (PAN) involvement is considered an advanced disease, the clinical characteristics of it have not been comprehensively elucidated. We reviewed the medical records of 1,277 patients received palliative chemotherapy with advanced gastric cancer according to metastatic sites: PAN-only metastasis, single organ metastasis other than PAN, and multiple organ metastasis. Time to other organ metastasis (TTOM) was determined only in PAN-only metastasis group as the time interval between initial diagnosis of recurrence or de novo metastasis and confirming distant metastasis beyond PAN area. The median overall survival (OS) of patients with PAN-only metastasis was significantly longer than that of patients with single organ metastasis other than PAN or multiple organ metastasis (13.8 months vs. 11.4 months vs. 8.4 months; P < 0.001). In the PAN-only metastasis group, patients with recurrent diseases showed longer TTOM beyond the PAN area (10.7 vs. 7.7 months; P = 0.037) and OS (23.8 vs. 12.8 months; P = 0.010) than those with de novo metastatic disease and it was validated by multivariate analysis. Patients with isolated PAN metastasis showed an excellent prognosis compared with patients with metastasis at other sites and it was primarily evident in patients with recurrent PAN metastasis.