e14016
Background: The increasing overall survival in cancer patients, due to advances in diagnostics and treatments, lead to an expected increase in diagnoses of brain metastasis (BM). A relevant ...feature in care-management of this special population is the safety in anticoagulant therapies administration, since cancer-associated thrombosis (CAT) is a concrete complication in patients with BM. In BM patients the risk of developing AEs increase with local treatments (i.e. radiation), and bleeding is a critical issue. Hence, understanding the risk/benefit ratio of anticoagulants in BM is mandatory. We conduct an observational, retrospective study collecting data from patients with BM diagnosis who underwent anti-cancer treatment and had at least a 3 months follow-up. We collect clinical characteristics, treatment, outcome, AEs concomitant medication with a focus on anticoagulants. Finally we assess the correlations between cardiovascular risk factors and increasing bleeding risk with anticoagulants. Methods: The study is observational, retrospective and single center. We included 148 patients with radiological evidence of BM who have at least 3 months follow-up after BM diagnosis. Patients were in charge of Medical Oncology Unit in Careggi University Hospital between 2015 and 2022. Data were collected from medical records. Results: We collected data from 148 patients with BM. Primary cancers were NSCLC (66%; n=98), breast (11%) and melanoma (6%) among the most common. Of the patients described, 87% (n=129) had an ECOG PS 0-1 and clinical condition was complicated by comorbidities as per hypertension (45%), COPD (15%) and diabetes (13%). Radiation was the most locoregional treatments performed (78%; n=115). Patients undergoing systemic treatments, had chemotherapy (51%), immunotherapy (24%) and TKIs (12%) after diagnosis of BM, and a DCR of 75% was achieved. 34% of patients with BM in NSCLC received anticoagulants therapy (n=33). Patients underwent LMWH (n=18) and fondaparinux (n=12), while NAOs were less common (n=5). The treatment goal was VTE prophylaxis, treatment of VTE or PTE respectively in 24% of patients; in 21% of patients anticoagulants were administered as prevention of AF complications. Regarding AEs, there were only one episode of minor hemorrhage (associated with NAO). Although statistical significance was not reached, we highlight a trend between VTE and hypertension in NSCLC population ( p=0.069) and between VTE and smoking history ( p=0.056) in the total population with BM. Conclusions: The use and safety of anticoagulant treatments in patients with BM have recently gained considerable importance. Our data do not allow us to draw conclusions about the safety of using NAOs or LMWHs in a population with BM. The retrospective nature and smallness of our sample suggest the need for further population studies with larger samples.
e16314
Background: Pancreatic adenocarcinoma (PC) is one of the big killers with a 5-year disease-free survival (DFS) rate of 19-26% after resection despite adjuvant treatments. KRAS mutations have ...been reported in approximately 90% of PC cases and, beyond KRAS activation by gene mutations, several miRNAs directly targeting KRAS have been reported to be simultaneously downregulated, strengthening the already activated RAS signaling. In addition, the interplay between miRNAs and RAS includes downstream miRNA effectors whose role needs to be elucidated. The aim of this study was to evaluate the expression of candidate miRNAs strictly related to KRAS expression in order to elucidate the prognostic value. Methods: In this single-center observational prospective study we included patients with pathologically confirmed PC, who underwent radical surgery and were referred to the Clinical Oncology Unit, Careggi University Hospital, Florence (Italy), between 2015 and 2022. Total RNA was extracted from FFPE sections, retro-transcribed and the resulting cDNA was then used for qPCR analysis. Results: Among 44 patients included in the study, 34.1% were male and 65.9% female (median age 75 years). The majority of cases had the primary tumor located at the head of the pancreas (65.9%) and the pathological stage was pT1-2 in 45.5%, pT3 in 54.5%, pN0 in 22.7%, pN+ in 77.3%. Overall, 63.6% of patients received adjuvant chemotherapy and 69.0% experienced disease recurrence. Twenty-three specimens were adequate for miRNA analysis. A different expression of the three target miRNAs between PC and healthy tissue was observed: miR-155 was overexpressed and miR-206 downregulated in PC, while miR-143 had a similar expression in both tissues. miR-143 overexpression was associated with nodal involvement (pN+) at the pathological examination (p = 0.029). Among clinicopathological features, pN+ was associated with shorter DFS (p = 0.009) and overall survival (OS) (p = 0.021) compared to pN0. A trend toward inferior DFS was observed for higher expression of miR-206 (p = 0.095) and miR-143 (p = 0.092). Among patients receiving a first-line treatment for advanced disease, miR-155 was overexpressed in responders vs non-responders (p = 0.048). Conclusions: miRNA expression is involved in tumorigenesis and metastatic spread in PC. A comprehensive analysis of the miRNA-RAS interplay deserves to be further investigated as a predictor of clinical outcome, especially for miR-143 overexpression which was associated with lymphatic spread and, consequently, poor prognosis.
Solitary fibrous tumor/hemangiopericytoma with primary tumor location in the central nervous system accounts for less than 1% of all central nervous system tumors. Despite the relatively indolent ...clinical course, extracranial metastases are reported in 28% of cases. In recent years, NAB2-STAT6 gene fusion has been recognized as the pathognomonic molecular feature of solitary fibrous tumor/hemangiopericytoma and STAT6 immunohistochemistry has been shown to be a sensitive and specific surrogate for the identification of the gene fusion in these patients. Here we report two cases of patients who experienced occurrence of diffuse extracranial metastases several years after successful surgery for an intracranial solitary fibrous tumor/hemangiopericytoma. In the first patient, the metastases had maintained similar histological features to the primary tumor; in contrast, in the second case, a dedifferentiation occurred with loss of expression of CD34 and Bcl-2. These different histological features were associated with radically different behaviors. Whereas the first case experienced an indolent course of the disease, the second patient had a rapid disease progression and deterioration of clinical conditions. The molecular imaging findings in these two cases and the role of functional imaging for tumor detection, disease staging and monitoring in this rare cancer are also discussed. Recurrences and metastases maintained high expression of somatostatin receptors confirmed by somatostatin receptor imaging in the first case. In contrast, in the second patient, the abrupt transition into a highly aggressive form was associated with the absence of somatostatin receptors at 111In Pentetreotide scan and intense hypermetabolism at 18F-FDG PET.
Background
The TOPAZ‐1 phase III trial reported a survival benefit with the anti‐programmed death cell ligand 1 (anti‐PD‐L1) durvalumab in combination with gemcitabine and cisplatin in patients with ...advanced biliary tract cancer. The present study investigated the efficacy and safety of this new standard treatment in a real‐world setting.
Methods
The analysed population included patients with unresectable, locally advanced or metastatic adenocarcinoma of the biliary tract treated with durvalumab in combination with gemcitabine and cisplatin at 17 Italian centres. The primary endpoint of the study was progression‐free survival (PFS), whereas secondary endpoints included overall survival (OS), overall response rate (ORR) and safety. Unadjusted and adjusted hazard ratios (HRs) by baseline characteristics were calculated using the Cox proportional hazards model.
Results
From February 2022 to November 2022, 145 patients were enrolled. After a median follow‐up of 8.5 months (95% CI: 7.9–13.6), the median PFS was 8.9 months (95% CI: 7.4–11.7). Median OS was 12.9 months (95% CI: 10.9–12.9). The investigator‐assessed confirmed ORR was 34.5%, and the disease control rate was 87.6%. Any grade adverse events (AEs) occurred in 137 patients (94.5%). Grades 3–4 AEs occurred in 51 patients (35.2%). The rate of immune‐mediated AEs (imAEs) was 22.7%. Grades 3–4 imAEs occurred in 2.1% of the patients. In univariate analysis, non‐viral aetiology, ECOG PS >0 and NLR ≥3 correlated with shorter PFS.
Conclusion
The results reported in this first real‐world analysis mostly confirmed the results achieved in the TOPAZ‐1 trial in terms of PFS, ORR and safety.
To investigate the impact of natremia in metastatic colorectal cancer (mCRC) patients treated with aflibercept plus folinic acid, 5-fluorouracil, oxaliplatin and irinotecan (FOLFIRI).
A total of 84 ...mCRC patients receiving aflibercept plus FOLFIRI as second-line treatment were enrolled and divided into two groups based on their median sodium value. Progression-free survival and overall survival were analyzed.
Patients with sodium levels ≥140 mEq/l had significantly longer median progression-free survival (4.1 vs 2 months; p < 0.01) and median overall survival (12 vs 7.3 months; p < 0.01) compared with those with lower levels.
This study suggests that higher pretreatment serum sodium levels are associated with improved outcomes in mCRC patients receiving aflibercept and FOLFIRI, potentially serving as a prognostic marker to aid treatment management.
TAS-102 is a preconstituted drug combination comprising an oral fluoropyrimidine (trifluridine, TFT) and a potent inhibitor of thymidine phosphorylase (tipiracil hydrochloride, TPI). TFT/TPI has ...recently received Food and Drug Administration (FDA) approval also for the treatment of gastric cancer after at least two lines of chemotherapy. The approval was based on a large phase 3 trial (TAGS), in which TAS-102 showed a 31 % decrease in the risk of death compared with placebo. Here, we review the pharmacological properties, clinical development and potential future directions of TAS-102 in gastric cancer.
Epithelioid hemangioendothelioma (EHE) is an extremely rare vascular sarcoma with an unpredictable clinical behavior. Pleural EHEs have been associated with poor response to treatment and reduced ...survival. To date, no standard treatment for EHE is available. Here we report the case of a 53-year-old man who underwent radical surgery for a symptomatic primary pleural EHE. Clinical presentation was characterized by chronic pain in the left hemithorax with transitory flare, anemia, weight loss and progressive worsening of clinical conditions. After surgery, he resumed active life and normal daily activities and, at 8 months, 18F-FDG PET and computed tomography scan showed no radiological evidence of recurrent disease. Clinical signs of this rare disease, histological features, imaging findings and functional imaging are discussed. We also report a summary of other cases with resected pleural EHE and we briefly review the role of chemotherapeutic, immunomodulatory and antiangiogenic drugs for advanced disease.
3568
Background: Encorafenib and cetuximab (EC) is the standard of care for pre-treated patients (pts) with BRAF V600E mut mCRC. DpR and ETS previously showed a strong correlation with survival ...outcomes in mCRC pts receiving 1
st
-line therapy. We assessed these tumour dynamic response parameters and their association with clinical outcome in pts with BRAF V600E mut mCRC treated with TT in second-line. Methods: Patients treated in a real-life setting with EC or EC plus binimetinib (ECB) in 20 Italian centres were included. Pts with measurable disease and at least one available disease reassessment by CT scan were eligible. Pts experiencing disease progression as best response (i.e. primary resistant) were not evaluable for DpR and ETS. Associations between DpR and ETS and progression free survival (PFS) and overall survival (OS) were tested by univariate and multivariate models. Results: 105 pts were included: 89 (85%) and 16 (15%) pts were treated with EC and ECB, respectively. Median PFS and OS were 5.2 and 10.3 mos, respectively. Twenty-nine pts (28%) were primary resistant, while 76 (72%) pts achieved disease control (51 48% and 25 24% pts had SD or CR/PR, respectively). Among baseline characteristics, the presence of peritoneal metastases was a predictor of primary resistance (p = 0.04). Among pts evaluable for response parameters (n = 76), median DpR was 15% and ETS occurred in 28 pts (37%). Mucinous histology was associated with a significantly lower magnitude of DpR (p = 0.005) and a lower rate of ETS (p = 0.002). A significant association between DpR and PFS was observed, both as a dichotomous ( ie, ≥ or < median value) and continuous variable in univariate and multivariate analyses. Also RECIST response correlated with PFS in the two models (table). DpR was associated with OS in the univariate analyses, but this was not confirmed in the multivariate models (table). No correlation between ETS and survival, either as a dichotomous ( ie, ≥ or < 20%) or a continuous variable, was observed. Conclusions: Having a DpR of at least 15% predicts longer PFS and OS in patients with BRAF V600E mut mCRC receiving TT as second-line treatment. An independent cohort of pts treated with second-line chemotherapy +/- antiangiogenic is under investigation as control group. Table: see text
Background
FLOT regimen is the standard perioperative treatment in Western countries for patients with locally advanced gastric (GC) or gastroesophageal junction cancer (GEJC). High microsatellite ...instability (MSI-H) and Mismatch Repair deficient (dMMR) demonstrated a favorable prognostic role and a concomitant negative predictive impact on the benefit of perioperative 5-fluorouracil-based doublets; however, its role in pts receiving FLOT chemotherapy is still unclear.
Methods
This is a retrospective, multicenter observational study of 265 pts with GC/GEJC treated with perioperative FLOT regimen in 11 Italian oncology centers between January 2017 to December 2021 and analyzed for microsatellite status.
Results
The MSI-H phenotype was found in 27 (10.2%) of 265 analyzed tumors. Compared to microsatellite stable (MSS) and Mismatch Repair proficient (pMMR) cases, MSI-H/dMMR were more frequently female (48.1% vs. 27.3%,
p
= 0.0424), elderly pts (age > 70 years, 44.4% vs. 13.4%,
p
= 0.0003), Laurens’s intestinal type (62.5% vs. 36.1%,
p
= 0.02) and pts with a primary location tumor in the antrum (37 vs. 14.3%,
p
= 0.0004). A statistically significant difference in the rate of pathologically negative lymph node emerged (63% vs 30.7%,
p
= 0.0018).
Compared to the MSS/pMMR tumor population, the MSI-H/dMMR subgroup had a better DFS (median not reached NR vs. 19.5 15.59–23.59 mos,
p
= 0.031) and OS (median NR vs. 34.84 26.68–47.60 mos,
p
= 0.0316).
Conclusions
These real-world data confirm that FLOT treatment is effective in daily clinical practice for locally advanced GC/GEJC, also in the MSI-H/dMMR subgroup. It also showed a higher rate of nodal status downstaging and a better outcome of MSI-H/dMMR pts in comparison to MSS/pMMR.
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