[Show abstract][Hide abstract] ABSTRACT: Yttrium-90 (Y90) radioembolization is an emerging strategy to treat liver malignancies, and clinical data supporting its use have accumulated in recent years. Y90-radioembolization has shown clinical effectiveness in intermediate and advanced hepatocellular carcinoma, with a favorable safety profile. Retrospective data show similar levels of effectiveness to transarterial chemoembolization in intermediate hepatocellular carcinoma, with some evidence of better tolerance. While phase 3 studies comparing Y90-radioembolization to chemoembolization in intermediate hepatocellular carcinoma would be difficult to conduct, studies comparing or combining Y90-radioembolization with sorafenib are under way. Questions also remain about the most suitable modalities for defining the dose to administer. Phase 3 studies are under way to clarify the place of Y90-radioembolization in the algorithm of HCC treatment.
[Show abstract][Hide abstract] ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC), which accounts for more than 90% of all pancreatic tumours, is a devastating malignancy. The prognosis is extremely poor because PDAC is usually a systemic disease at diagnosis. All stages, the survival does not exceed 5% at 5 years. However 15% of PDAC can be resected and today a margin-negative resection followed by adjuvant chemotherapy remains the only potential for a prolonged survival. Postoperative mortality had significantly decreased and the benefit of postoperative adjuvant chemotherapy has been clearly shown. Substantial progress has been made in the field of palliative chemotherapy by introducing new chemotherapy regimens (FOLFIRINOX [folinic acid, 5-fluorouracil, irinotecan and oxaliplatin] and gemcitabine/nab-paclitaxel), when the patient's performance status allows the use of these drugs. The role of radiation therapy remains controversial.
[Show abstract][Hide abstract] ABSTRACT: Pancreatic Ductal Adenocarcinoma (PDAC) is a disease with a great heterogeneity in the response to treatments. To improve the responsiveness to treatments there are two different approaches, the first one consist to develop new and more efficient drugs that intent to cure all patients and the second one is to use already-approved drugs, alone or in combination, but selecting beforehand the most sensitive patients. In this work we explored the efficiency of the second possibility. We developed a collection of 17 PDAC samples collected by Endoscopic Ultrasound-Guided Fine-Needle Aspiration (EUS-FNA) or surgery and preserved as xenografts and as primary cultures. This collection was characterized at molecular level by a transcriptomic analysis using an Affymetrix approach. In this paper we present data demonstrating that a subgroup of PDAC responds to low doses of 5-aza-dC. These tumors show a specific RNA expression profile that could serve as a marker, but there is no correlation with Dnmt1, Dnmt3A or Dnmt3B expression. Responder tumors corresponded to well-differentiated samples and longer survival patients. In conclusion, we present data obtained with the well-known drug 5-aza-dC as a proof of concept that a drug that seems to be inefficient in solid tumors in general could be applicable to a particular subgroup of patients with PDAC.
[Show abstract][Hide abstract] ABSTRACT: This study aimed to evaluate the long-term prognostic usefulness of (18)F-FDG PET for patients with metastatic gastroenteropancreatic neuroendocrine tumors (GEPNETs).
Journal of Nuclear Medicine 10/2014; 55(11). DOI:10.2967/jnumed.114.144386 · 5.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We report a 57-year-old male who was treated with high-dose danazol for hereditary angioedema for more than 30 years; he developed hepatocellular carcinoma in the absence of cirrhosis. Despite surgical resection, he had a recurrence and received sorafenib, but had a poor skin tolerance. Such tumors arising after danazol are infrequent, and this case is highly unique due to the minor lesions found on the liver.
Case Reports in Oncology 09/2014; 7(3):825-7. DOI:10.1159/000370106
[Show abstract][Hide abstract] ABSTRACT: Hepatocellular carcinoma (HCC)-closely associated with liver cirrhosis and, in fact, the main cause of death in patients with such disease-is now recognized as one of the most-prevalent and lethal neoplasms worldwide. Prognosis and allocation of the multiple available treatment options for patients with HCC are influenced not only by tumour stage, but also by the degree of liver-function impairment. Therefore, accurate assessment and classification of disease is important for patient management. According to the Barcelona Clinic Liver Cancer (BCLC) algorithm, intermediate-stage HCC is defined as extensive multifocal disease without vascular invasion in patients with preserved liver function and absence of cancer-related symptoms; in this context, transarterial chemoembolization (TACE) is considered the standard treatment. The use of drug-eluting beads has enabled standardization of this procedure, resulting in higher reproducibility and tolerability of the treatment. Nevertheless, not all patients with intermediate-stage HCC are good candidates for TACE and, for such patients in whom TACE is not appropriate or has failed, other treatments can be considered, including sorafenib. Radioembolization is a promising alternative that deserves further prospective studies. Herein, we review the current approaches used to accurately stratify patients with intermediate-stage HCC and subsequently allocate the most-appropriate treatments. The key developments in therapeutic strategies are also discussed.
[Show abstract][Hide abstract] ABSTRACT: Assessing treatment responses in hepatocellular carcinoma (HCC) is challenging, and alternative radiologic methods of measuring treatment response are required. Modified Response Evaluation Criteria in Solid Tumors (mRECIST) for HCC and alpha-fetoprotein (AFP) levels were assessed in a post hoc analysis of a phase II study of brivanib, a selective dual inhibitor of fibroblast growth factor and vascular endothelial growth factor signaling.
HCC patients were treated with first-line (cohort A; n = 55) or second-line (cohort B; n = 46) brivanib alaninate 800 mg once daily. Outcomes were compared between World Health Organization (WHO) criteria and (retrospectively by) mRECIST by independent review. The relationship between on-study AFP changes and outcome was analyzed in patients with elevated AFP at baseline.
Response rates were higher with mRECIST versus WHO criteria in cohorts A (25.5% vs. 7.3%) and B (10.9% vs. 4.3%). Progressive disease (PD) as assessed by mRECIST was associated with a very short median overall survival (OS; cohort A, 2.8 months; cohort B, 5.3 months); PD as assessed by WHO criteria reflected a mixed population of patients with better outcomes. mRECIST responders tended to have a>50% AFP decrease during therapy. In cohorts A and B pooled, an early AFP response (>20%or >50% decline from baseline within the first 4 weeks) was not associated with longer median OS.
Tumor response as assessed by mRECIST differed from that by WHO criteria, with mRECIST possibly identifying true nonresponders with a poor prognosis. Many patients had AFP decreases correlating with tumor shrinkage, yet an association with long-term benefit was unclear. mRECIST and on-treatment AFP levels are being explored further with brivanib in HCC.
[Show abstract][Hide abstract] ABSTRACT: The treatment of hepatocellular carcinoma (HCC) is difficult due to the underlying cirrhosis which has its own influence on therapeutic issues. An inquiry was performed in centres with specialized multidisciplinary team meetings dedicated to HCC (HCC-MTM) or in centres with non-specialized (digestive oncology or general oncology) multidisciplinary team meetings (NS-MTM). The number of cases of HCCs taken in charge yearly was significantly higher in HCC-MTM than in NS-MTM (p=0,0014). Interventional radiologists and transplant surgeons were more frequently implied in HCC-MTM than in NS-MTM (respectively p=0,009 and p=0,02). On site availability of every treatment of HCC was higher in RCP-MTM than in NS-MTM (p=0,015). There were no inclusion in clinical trials in 40.5 % of NS-MTM versus only 17.6 % of HCC-MTM (p=0,0086). In three clinical cases out of seven there were discrepancies between the therapeutic options of HCC-MTM and NS-MTM. In all three cases, the treatment offered to the patient by HCC-MTM was more consistent with clinical standards. These results prompt to perform more studies on the quality of management of patients with HCCs by MTMs.
Bulletin du cancer 06/2014; 101(6). DOI:10.1684/bdc.2014.1918 · 0.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: Although the prevalence of esophageal cancer increases in elderly patients, its clinical history and outcome after treatment remain poorly described.
Methods: Between January 2001 and December 2011, 58 patients (pts) older than 75 years received 3D-conformal radiotherapy (mean dose 51 Gy) in two French cancer centers. 47/58 (82%) patients received concomitant chemotherapy (with CDDP and/or FU regimens) and 8 patients underwent surgery after primary radiochemotherapy (RCT).
Results: Median age was 77.9 years and the performance status (PS) was 0 or 1 in 89%. Tumors were mainly adenocarcinoma of lower esophagus or gastroesophageal junction (n = 51, 89%), T3T4 (n = 54, 95%), and N1 (n = 44, 77%). The mean follow-up was 21.9 months. In the overall population, the median progression-free survival was 9.6 months and median overall survival (OS) was 14.5 months. Using univariate analysis, OS was significantly associated with age (p = 0.048), PS (p < 0.001), and surgery (p = 0.035). 35 (60.3%) and 18 patients (31%) experienced grade 1–2 or 3–4 toxicity, respectively (CTCAE v4.0).
Conclusion: Radiochemotherapy in elderly patients is a feasible treatment and its outcome is close to younger patient’s outcome published in the literature. Surgical resection, after comprehensive geriatric assessment, should be recommended as the standard treatment for adenocarcinoma of lower esophagus or gastroesophageal junction in elderly patients with good PS and low co-morbidity profile, as it is in younger patients.
Frontiers in Oncology 05/2014; 4:100. DOI:10.3389/fonc.2014.00100
[Show abstract][Hide abstract] ABSTRACT: We report the case of a 57-year-old man who was diagnosed with a large unresectable cholangiocarcinoma associated with 2 satellite nodules and without clear margins with the right hepatic vein. Despite 4 cycles of GEMOX (stopped due to a hypertransaminasemia believed to be due to gemcitabine) and 4 cycles of FOLFIRINOX, the tumor remained stable and continued to be considered unresectable. Radioembolization (resin microspheres, SIRS-spheres(®)) targeting the left liver (474 MBq) and segment IV (440 MBq) was performed. This injection was very well tolerated, and 4 more cycles of FOLFIRINOX were given while waiting for radioembolization efficacy. On computed tomography scan, a partial response was observed; the tumor was far less hypervascularized, and a margin was observed between the tumor and the right hepatic vein. A left hepatectomy enlarged to segment VIII was performed. On pathological exam, most of the tumor was acellular, with dense fibrosis around visible microspheres. Viable cells were observed only at a distance from beads. Radioembolization can be useful in the treatment of cholangiocarcinoma, allowing in some cases a secondary resection.
World Journal of Gastroenterology 05/2014; 20(17):5131-4. DOI:10.3748/wjg.v20.i17.5131 · 2.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In Europe, trans-arterial chemoembolization (TACE) is usually given to patients with Barcelona Clinic Liver Cancer (BCLC) "intermediate stage" hepatocellular carcinoma (HCC), and is associated with a modest improvement in median overall survival. In the two positive randomized trials that have been reported, TACE was stopped in cases of severe toxicity, worsening of liver cirrhosis or performance status and tumor progression, including local progression, extrahepatic spread and portal vein thrombosis. The necessity to stop TACE leads to the concept of untreatable progression, which is characterized by massive liver involvement, extrahepatic spread, vascular invasion, impaired liver function or performance status. More recently, the assessment for re-treatment with TACE (ART) score has been developed to determine which patients will not benefit from a second or a third TACE therapy. Herein, we propose an algorithm that summarizes our experience with TACE.
[Show abstract][Hide abstract] ABSTRACT: We herein report the case of a 73-year-old woman who developed skin and nail disorders 2 months before her digestive symptoms started, which lead to the diagnosis of gastric adenocarcinoma. The lesions were diagnosed as Bazex syndrome, usually seen in squamous cell carcinoma. Under systemic chemotherapy, the cutaneous signs improved for some months before worsening when the disease progressed.
Case Reports in Oncology 04/2014; 7(1):285-7. DOI:10.1159/000362787
[Show abstract][Hide abstract] ABSTRACT: Background
Definitive chemoradiotherapy is a curative treatment option for oesophageal carcinoma, especially in patients unsuitable for surgery. The PRODIGE5/ACCORD17 trial aimed to assess the efficacy and safety of the FOLFOX treatment regimen (fluorouracil plus leucovorin and oxaliplatin) versus fluorouracil and cisplatin as part of chemoradiotherapy in patients with localised oesophageal cancer.
We did a multicentre, randomised, open-label, parallel-group, phase 2/3 trial of patients aged 18 years or older enrolled from 24 centres in France between Oct 15, 2004, and Aug 25, 2011. Eligible participants had confirmed stage I–IVA oesophageal carcinoma (adenocarcinoma, squamous-cell, or adenosquamous), Eastern Cooperative Oncology Group (ECOG) status 0–2, sufficient caloric intake, adequate haematological, renal, and hepatic function, and had been selected to receive definitive chemoradiotherapy. Patients were randomly assigned (1:1) to receive either six cycles (three concomitant to radiotherapy) of oxaliplatin 85 mg/m2, leucovorin 200 mg/m2, bolus fluorouracil 400 mg/m2, and infusional fluorouracil 1600 mg/m2 (FOLFOX) over 46 h, or four cycles (two concomitant to radiotherapy) of fluorouracil 1000 mg/m2 per day for 4 days and cisplatin 75 mg/m2 on day 1. Both groups also received 50 Gy radiotherapy in 25 fractions (five fractions per week). Random allocation to treatment groups was done by a central computerised randomisation procedure by minimisation, stratified by centre, histology, weight loss, and ECOG status, and was achieved independently from the study investigators. The primary endpoint was progression-free survival. Data analysis was primarily done by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00861094.
134 participants were randomly allocated to the FOLFOX group and 133 to the fluorouracil and cisplatin group (intention-to-treat population), and 131 patients in the FOLFOX group and 128 in the fluorouracil and cisplatin group actually received the study drugs (safety population). Median follow-up was 25·3 months (IQR 15·9–36·4). Median progression-free survival was 9·7 months (95% CI 8·1–14·5) in the FOLFOX group and 9·4 months (8·1–10·6) in the fluorouracil and cisplatin group (HR 0·93, 95% CI 0·70–1·24; p=0·64). One toxic death occurred in the FOLFOX group and six in the fluorouracil–cisplatin group (p=0·066). No significant differences were recorded in the rates of most frequent grade 3 or 4 adverse events between the treatment groups. Of all-grade adverse events that occurred in 5% or more of patients, paraesthesia (61 [47%] events in 131 patients in the FOLFOX group vs three [2%] in 128 patients in the cisplatin–fluorouracil group, p<0·0001), sensory neuropathy (24 [18%] vs one [1%], p<0·0001), increases in aspartate aminotransferase concentrations (14 [11%] vs two [2%], p=0·002), and increases in alanine aminotransferase concentrations (11 [8%] vs two [2%], p=0·012) were more common in the FOLFOX group, whereas serum creatinine increases (four [3%] vs 15 [12%], p=0·007), mucositis (35 [27%] vs 41 [32%], p=0·011), and alopecia (two [2%] vs 12 [9%], p=0·005) were more common in the fluorouracil and cisplatin group.
Although chemoradiotherapy with FOLFOX did not increase progression-free survival compared with chemoradiotherapy with fluorouracil and cisplatin, FOLFOX might be a more convenient option for patients with localised oesophageal cancer unsuitable for surgery.
UNICANCER, French Health Ministry, Sanofi-Aventis, and National League Against Cancer.
The Lancet Oncology 03/2014; 15(3). DOI:10.1016/S1470-2045(14)70028-2 · 24.73 Impact Factor