Search

Background Different histological growth patterns (HGP) describing the tumor-to-liver interface have been described in colorectal liver metastases and have been associated with a strong prognostic value. However, HGP of peritoneal metastases (PM) of colorectal cancer (CRC) have not yet been described. Our objective was to determine whether distinct HGP can be identified in PMCRC and to evaluate their potential prognostic value in these patients. Methods This retrospective study included 38 patients who underwent curative-intent surgery for PMCRC between July 2012 and March 2019, with PCI≤6, and who had not received preoperative chemotherapy. In each patient, the tumor-to-peritoneum interface was evaluated in the excised peritoneal nodules. The association between HGP and postoperative survival was analyzed by using the Kaplan–Meier method. Results Two distinct HGP were identified: a pushing-type (P-HGP), characterized by a fibrous rim separating the PM and peritoneum, and an infiltrating-type (I-HGP), characterized by focal penetration of tumor cells into the surrounding peritoneal lining without a fibrous rim. Fifteen patients had dominant P-HGP, and 23 patients had dominant I-HGP. Patients with dominant P-HGP (>50% tumor-peritoneum interface) had a significantly better DFS (30 months) than those with P-HGP p = 0.029). Patients with a P-HGP dominance >60% had better OS (131 months) than those with P-HGP p = 0.044). Conclusions This is the first description of two distinct, reproducible HGP in PMCRC. The dominant P-HGP is associated with a favorable prognosis in patients with PMCRC, compared with I-HGP, suggesting that this parameter could ultimately represent a new prognostic biomarker.

Body composition parameters including muscle and adipose tissue measurements have emerged as prognostic factors in cancer patients. Besides cell cycle regulation, CDK 4 and 6 also control metabolic processes (lipid synthesis, glycolysis, and mitochondrial function). We studied the impact of baseline body composition parameters on response to CDK 4/6 inhibition and changes on body composition during treatment. Retrospective study of 50 patients treated at Institut Jules Bordet between December 2016 and August 2019 with endocrine therapy and CDK 4/6 inhibitor as first or second-line treatment for metastatic breast cancer (BC). CT-based body composition analysis was performed at 3 time points. Cox regression and Kaplan–Meier method were used for the association with Progression-free survival (PFS). Changes in body composition parameters were described in means and compared using paired sampled T test. Baseline sarcopenia was present in 40% of patients and associated with a significantly worse PFS compared to patients without sarcopenia (20.8 vs 9.6 months, HR 2.52; 95% CI 1.02–6.19, p = 0.037). Patients with higher visceral fat index and higher visceral fat density had better PFS (20.8 vs 10.4 months, HR 0.40; 95% CI 0.16–0.99 p = 0.041-stratified for treatment line). No significant alterations in body composition parameters during treatment were observed. Sarcopenia is a potential early marker of poor prognosis among patients with metastatic BC treated with CDK 4/6 inhibitors. CT scan evaluation of sarcopenia and adiposity revealed significant prognostic information. Visceral fat could also play an important role in response to CDK 4/6 inhibitors, deserving further investigation.

Purpose: Reported outcomes of patients with intra-hepatic cholangiocarcinoma (IH-CCA) treated with radioembolization are highly variable, which indicates differences in included patients’ characteristics and/or procedure-related variables. This study aimed to identify patient- and treatment-related variables predictive for radioembolization outcome. Methods: This retrospective multicenter study enrolled 58 patients with unresectable and chemorefractory IH-CCA treated with resin 90Y-microspheres. Clinicopathologic data were collected from patient records. Metabolic parameters of liver tumor(s) and presence of lymph node metastasis were measured on baseline 18F-FDG-PET/CT. 99mTc-MAA tumor to liver uptake ratio (TLRMAA) was computed for each lesion on the SPECT-CT. Activity prescription using body-surface-area (BSA) or more personalized partition-model was recorded. The study endpoint was overall survival (OS) starting from date of radioembolization. Statistical analysis was performed by the log-rank test and multivariate Cox’s proportional hazards model. Results: Median OS (mOS) post-radioembolization of the entire cohort was 10.3 months. Variables associated with significant differences in terms of OS were serum albumin (hazard ratio (HR) = 2.78, 95%CI:1.29–5.98, p = 0.002), total bilirubin (HR = 2.17, 95%CI:1.14–4.12, p = 0.009), aspartate aminotransferase (HR = 2.96, 95%CI:1.50–5.84, p < 0.001), alanine aminotransferase (HR = 2.02, 95%CI:1.05–3.90, p = 0.01) and γ-GT (HR = 2.61, 95%CI:1.31–5.22, p < 0.001). The presence of lymph node metastasis as well as a TLRMAA < 1.9 were associated with shorter mOS: HR = 2.35, 95%CI:1.08–5.11, p = 0.008 and HR = 2.92, 95%CI:1.01–8.44, p = 0.009, respectively. Finally, mOS was significantly shorter in patients treated according to the BSA method compared to the partition-model: mOS of 5.5 vs 14.9 months (HR = 2.52, 95%CI:1.23–5.16, p < 0.001). Multivariate analysis indicated that the only variable that increased outcome prediction above the clinical variables was the activity prescription method with HR of 2.26 (95%CI:1.09–4.70, p = 0.03). The average mean radiation dose to tumors was significantly higher with the partition-model (86Gy) versus BSA (38Gy). Conclusion: Radioembolization efficacy in patients with unresectable recurrent and/or chemorefractory IH-CCA strongly depends on the tumor radiation dose. Personalized activity prescription should be performed., SCOPUS: ar.j, info:eu-repo/semantics/published

Introduction: Recommended treatment for locally advanced rectal cancer (LARC) is neoadjuvant chemoradiotherapy (NACRT) followed by surgery and total mesorectal excision (TME). The role of adjuvant chemotherapy (ACT) in this regimen is still debated. Assessment of Dworak’s tumor regression grade (TRG) after NACRT could potentially select patients who might benefit from ACT. Materials and methods: Data for patients who underwent NACRT and TME for LARC between 2007 and 2014 were retrieved from the Bordet Institute database. Overall survival (OS) and disease-free survival (DFS) were calculated for the whole population, according to whether or not they received ACT, and according to TRG. Results: We included 74 patients (38 males) with a median age of 62.7 years (33–84 years). AJCC stage cIIIb disease was the most frequent (73%). Pathologic complete response (pCR) was achieved in 13 patients (17.6%). ACT was administered to 42 patients (56.8%). Five-year OS and DFS of patients who received ACT or not were 92 and 84.5% (p = ns), and 79.9 and 84.8% (p = ns), respectively. OS was related to TRG (cut-off value of 3) (p = 0.001). ACT administration was not correlated with improved outcomes in any TRG groups. Conclusion: TRG is a prognostic factor for both OS and DFS but does not appear to have a significant benefit for the selection of patients with LARC treated with NACRT who might benefit from the administration of ACT. Prospective randomized trials with larger populations are needed to identify factors that predict which patients may benefit from the administration of ACT., SCOPUS: ar.j, info:eu-repo/semantics/published

Background: The prognostic value of body composition in cancer patients has been widely studied during the last decade. The main finding of these studies is that sarcopenia, or skeletal muscle depletion, assessed by CT imaging correlates with a reduced overall survival (OS). By contrast, the prognostic value of fat mass remains ill-defined. This study aims to analyze the influence of body composition including both muscle mass and adipose tissue on OS in a homogeneous population of advanced colorectal cancer (CRC) patients. Methods: Among 235 patients with chemorefractory advanced CRC included in the SoMore and RegARd-C trials, body composition was assessed in 217 patients on baseline CT images. The relationship between body composition (sarcopenia, muscle density, subcutaneous and visceral fat index and density), body mass index (BMI) and OS were evaluated. Results: Patients with a higher BMI had a better OS (≥30 versus < 30, HR: 0.50; 0.33-0.76). Those with low muscle index and muscle density had an increased mortality (HR: 2.06; 1.45-2.93 and HR: 1.54; 1.09-2.18, respectively). Likewise, low subcutaneous and visceral fat index were associated with an increased risk of dying (HR: 1.63; 1.23-2.17 and 1.48; 1.09-2.02 respectively), as were a high subcutaneous and visceral adipose tissue density (HR: 1.93; 1.44-2.57 and 2.40; 1.79-3.20 respectively). In multivariate analysis, a high visceral fat density was the main predictor of poor survival. Conclusions: Our results confirm the protective role of obesity in CRC patients at an advanced stage, as well as the negative prognostic impact of muscle depletion on survival. More importantly, our data show for the first time that visceral adipose tissue density is an important prognostic factor in metastatic CRC. Trial registration: NCT01290926, 07/02/2011 and NCT01929616, 28/08/2013., SCOPUS: ar.j, info:eu-repo/semantics/published

BAY 43-9006 is a novel dual-action Raf kinase and vascular endothelial growth factor receptor (VEGFR) inhibitor that targets tumour cell proliferation and tumour angiogenesis. This Phase I study was undertaken to determine the safety profile, maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), pharmacokinetics, and tumour response profile of oral BAY 43-9006 in patients with advanced, refractory solid tumours. BAY 43-9006 was administered daily for repeated cycles of 21 days on/7 days off. A total of 44 patients were enrolled at doses from 50 to 800 mg b.i.d. Pharmacokinetic profiles of BAY 43-9006 in plasma were determined during the first treatment cycle. The most frequently reported adverse events over multiple cycles were gastrointestinal (75%), dermatologic (71%), constitutional (68%), pain (64%), or hepatic (61%) related. A MTD of 400 mg b.i.d. BAY 43-9006 was defined. BAY 43-9006 was absorbed rapidly; steady-state conditions were reached within 7 days. BAY 43-9006 exposure increased nonproportionally with increasing dose. In all, 32 patients were evaluated for tumour response: 15 patients showed tumour progression, 16 patients experienced stable disease (>6 months in eight patients), and one patient with renal cell carcinoma achieved a partial response. BAY 43-9006 given for 21 days with 7 days off treatment was safe, well tolerated, and showed antitumour activity., Clinical Trial, Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't, info:eu-repo/semantics/published