[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.
[show abstract][hide abstract] ABSTRACT: Hepatocellular carcinoma is generally diagnosed at advanced stages, for which only palliative treatments are possible by intra-arterial route or by targeted therapies. Among these treatments, metabolic radiotherapy using (90)-yttrium or (188)Re and sorafenib are two options adopted in monotherapy.
We address the question of a possible synergy arising from the combination of these two treatments. Two primary malignant hepatoma cell lines, N1S1 (murine HCC) and HepG2 (human hepatoblastoma) were treated in media containing increasing concentrations of sorafenib with/without (188)Re to assess the cellular toxicities of each treatment alone and in combination. The combination index method was used to look for synergy or additivity.
A synergistic advantage of a treatment combining (188)Re and sorafenib is shown in vitro on hepatoma cell lines.
This combined approach is promising and now needs to be confirmed by more complex in vitro models integrating the tumoral stroma, as well as by in vivo studies.
Anticancer research 09/2013; 33(9):3871-7. · 1.71 Impact Factor
[show abstract][hide abstract] ABSTRACT: Brivanib is a dual inhibitor of vascular-endothelial growth factor and fibroblast growth factor receptors that are implicated in the pathogenesis of hepatocellular carcinoma (HCC). Our multinational, randomized, double-blind, phase III trial compared brivanib with sorafenib as first-line treatment for HCC.
Advanced HCC patients who had no prior systemic therapy were randomly assigned (ratio, 1:1) to receive sorafenib 400 mg twice daily orally (n = 578) or brivanib 800 mg once daily orally (n = 577). Primary end point was overall survival (OS). Secondary end points included time to progression (TTP), objective response rate (ORR), disease control rate (DCR) based on modified Response Evaluation Criteria in Solid Tumors (mRECIST), and safety.
The primary end point of OS noninferiority for brivanib versus sorafenib in the per-protocol population (n = 1,150) was not met (hazard ratio [HR], 1.06; 95.8% CI, 0.93 to 1.22), based on the prespecified margin (upper CI limit for HR ≤ 1.08). Median OS was 9.9 months for sorafenib and 9.5 months for brivanib. TTP, ORR, and DCR were similar between the study arms. Most frequent grade 3/4 adverse events for sorafenib and brivanib were hyponatremia (9% and 23%, respectively), AST elevation (17% and 14%), fatigue (7% and 15%), hand-foot-skin reaction (15% and 2%), and hypertension (5% and 13%). Discontinuation as a result of adverse events was 33% for sorafenib and 43% for brivanib; rates for dose reduction were 50% and 49%, respectively.
Our study did not meet its primary end point of OS noninferiority for brivanib versus sorafenib. However, both agents had similar antitumor activity, based on secondary efficacy end points. Brivanib had an acceptable safety profile, but was less well-tolerated than sorafenib.
Journal of Clinical Oncology 08/2013; · 18.04 Impact Factor
[show abstract][hide abstract] ABSTRACT: Brivanib is a selective dual inhibitor of vascular endothelial growth factor and fibroblast growth factor receptors implicated in tumorigenesis and angiogenesis in hepatocellular carcinoma (HCC). An unmet medical need persists for patients with HCC whose tumors do not respond to sorafenib or who cannot tolerate it. This multicenter, double-blind, randomized, placebo-controlled trial assessed brivanib in patients with HCC who had been treated with sorafenib.
In all, 395 patients with advanced HCC who progressed on/after or were intolerant to sorafenib were randomly assigned (2:1) to receive brivanib 800 mg orally once per day plus best supportive care (BSC) or placebo plus BSC. The primary end point was overall survival (OS). Secondary end points included time to progression (TTP), objective response rate (ORR), and disease control rate based on modified Response Evaluation Criteria in Solid Tumors (mRECIST) and safety.
Median OS was 9.4 months for brivanib and 8.2 months for placebo (hazard ratio [HR], 0.89; 95.8% CI, 0.69 to 1.15; P = .3307). Adjusting treatment effect for baseline prognostic factors yielded an OS HR of 0.81 (95% CI, 0.63 to 1.04; P = .1044). Exploratory analyses showed a median time to progression of 4.2 months for brivanib and 2.7 months for placebo (HR, 0.56; 95% CI, 0.42 to 0.76; P < .001), and an mRECIST ORR of 10% for brivanib and 2% for placebo (odds ratio, 5.72). Study discontinuation due to treatment-related adverse events (AEs) occurred in 61 brivanib patients (23%) and nine placebo patients (7%). The most frequent treatment-related grade 3 to 4 AEs for brivanib included hypertension (17%), fatigue (13%), hyponatremia (11%), and decreased appetite (10%).
In patients with HCC who had been treated with sorafenib, brivanib did not significantly improve OS. The observed benefit in the secondary outcomes of TTP and ORR warrants further investigation.
Journal of Clinical Oncology 08/2013; · 18.04 Impact Factor
[show abstract][hide abstract] ABSTRACT: Hepatocellular carcinoma (HCC) is a complex disease with a poor prognosis. Incidence and mortality rates are increasing in many geographical regions, indicating a need for better management strategies. Among several risk factors for HCC, the most common are cirrhosis because of chronic hepatitis B virus or hepatitis C virus infection and alcohol consumption, obesity, and diabetes. In some patients, combined risk factors present additional challenges to the prevention and treatment of HCC. Screening and surveillance of high-risk populations varies widely by geographic regions, and access to optimal surveillance is critical for early diagnosis. The treatment choice for HCC depends on the cancer stage, patient performance status, and liver function and requires a multidisciplinary approach and close cooperation among specialists for the best patient outcomes. Despite advances in surgical treatments and locoregional therapies, recurrence and liver failure remain significant challenges. The pathogenesis of HCC is a multistep and complex process, wherein angiogenesis plays an important role. The multikinase inhibitor sorafenib is the only approved targeted agent for advanced HCC, although promising results have been obtained with other targeted agents and combinations, and the results of ongoing trials are eagerly awaited. Clinical trials with rigorous study designs, including molecular classification and validation of new molecular biomarkers, are required to improve the personalized treatment of HCC. This article provides an overview of HCC and was developed through a review of relevant literature, clinical trial data, and updated clinical guidelines.
European journal of gastroenterology & hepatology 06/2013; 25(6):639-651. · 1.66 Impact Factor
[show abstract][hide abstract] ABSTRACT: BACKGROUND: Contralateral hypertrophy after (90)Y radioembolization has been described in case reports, but the incidence and quantitative extent of liver volume modifications after this therapy are unknown. METHODS: This retrospective study examined patients with hepatocellular carcinoma and underlying cirrhosis treated by (90)Y radioembolization. The main inclusion criteria were unilateral treatment, no prior liver surgery, and computed tomographic scans allowing for volumetric assessments. Treated, tumor, and contralateral liver volumes were measured. Whole liver volume and the ratio of contralateral to total functional liver volume after a virtual hepatectomy were calculated. RESULTS: Data of 34 patients were analyzed. Response rates were 26 % according to Response Evaluation Criteria in Solid Tumors (RECIST) and 63 % according to modified RECIST. Median overall survival was 13.5 months. Median treated volume decreased from 938 mL (interquartile range [IQR] = 719) to 702 mL (IQR = 656) (p < 0.001), while median contralateral volume increased from 724 mL (IQR = 541) to 920 mL (IQR = 530) (p < 0.001). The whole liver volume remained stable, with a median volume of 1,702 mL (IQR = 568) versus 1,577 mL (IQR 670), respectively (p = 0.55). The mean maximal increase in contralateral volume was 42 % (95 % confidence interval 16-67). Overall, 13 patients (38.2 %) exhibited increases greater than 30 %, while 13 patients (38.2 %) showed no increase or showed increases less than 10 %. The median ratio of contralateral to total functional liver volume increased from 48.5 to 64.9 % (p < 0.001), with the proportion of patients with a ratio of ≥50 % increasing from 47.1 to 67.6 % (p = 0.013). CONCLUSIONS: (90)Y radioembolization induced frequent and similar increases in functional liver remnant volume compared with portal vein embolization. This technique should be tested in a prospective study phase 2 study before liver resection.
Annals of Surgical Oncology 03/2013; · 4.12 Impact Factor
[show abstract][hide abstract] ABSTRACT: From the description of the clinical case of a patient consulting for chest pain sequelae after treatment of her breast cancer, we retain the diagnosis of myofascial pain of the serratus anterior. A literature review of pain sequelae of breast cancer is proposed and follows a proposal of what to do in order to retain the clinical diagnosis, often if we judge the results of a recent prospective study (44,8% of patients develop a remote myofascial pain treatment).
[show abstract][hide abstract] ABSTRACT: PURPOSETo compare the quality of life (QoL) of patients receiving oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX) or gemcitabine as first-line chemotherapy and to assess whether pretreatment QoL predicts survival in patients with metastatic pancreatic cancer.Patients And methodsThree hundred forty-two patients with performance status 0 or 1 were randomly assigned to receive FOLFIRINOX (oxaliplatin, 85 mg/m(2); irinotecan, 180 mg/m(2); leucovorin, 400 mg/m(2); and fluorouracil, 400 mg/m(2) bolus followed by 2,400 mg/m(2) 46-hour continuous infusion, once every 2 weeks) or gemcitabine 1,000 mg/m(2) weekly for 7 of 8 weeks and then weekly for 3 of 4 weeks. QoL was assessed using European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire C30 every 2 weeks.ResultsImprovement in global health status (GHS; P < .001) was observed in the FOLFIRINOX arm and improvement in emotional functioning (P < .001) was observed in both arms, along with a decrease in pain, insomnia, anorexia, and constipation in both arms. A significant increase in diarrhea was observed in the FOLFIRINOX arm during the first 2 months of chemotherapy. Time until definitive deterioration ≥ 20 points was significantly longer for FOLFIRINOX compared with gemcitabine for GHS, physical, role, cognitive, and social functioning, and six symptom domains (fatigue, nausea/vomiting, pain, dyspnea, anorexia, and constipation). Physical functioning, constipation, and dyspnea were independent significant prognostic factors for survival with treatment arm, age older than 65 years, and low serum albumin. CONCLUSIONFOLFIRINOX significantly reduces QoL impairment compared with gemcitabine in patients with metastatic pancreatic cancer. Furthermore, baseline QoL scores improved estimation of survival probability when added to baseline clinical and demographic variables.
Journal of Clinical Oncology 12/2012; · 18.04 Impact Factor
[show abstract][hide abstract] ABSTRACT: The Sorafenib Hepatocellular Carcinoma (HCC) Assessment Randomized Protocol (SHARP) trial demonstrated that sorafenib improves overall survival and is safe for patients with advanced HCC. In this trial, 602 patients with well-preserved liver function (>95% Child-Pugh A) were randomized to receive either sorafenib 400mg or matching placebo orally b.i.d. on a continuous basis. Because HCC is a heterogeneous disease, baseline patient characteristics may affect individual responses to treatment. In a comprehensive series of exploratory subgroup analyses, data from the SHARP trial were analyzed to discern if baseline patient characteristics influenced the efficacy and safety of sorafenib.
Five subgroup domains were assessed: disease etiology, tumor burden, performance status, tumor stage, and prior therapy. Overall survival (OS), time to progression (TTP), disease control rate (DCR), and safety were assessed for subgroups within each domain.
Subgroup analyses showed that sorafenib consistently improved median OS compared with placebo, as reflected by hazard ratios (HRs) of 0.50-0.85, similar to the complete cohort (HR=0.69). Sorafenib also consistently improved median TTP (HR, 0.40-0.64), except in HBV-positive patients (HR, 1.03), and DCR. Results are limited by small patient numbers in some subsets. The most common grade 3/4 adverse events included diarrhea, hand-foot skin reaction, and fatigue; the incidence of which did not differ appreciably among subgroups.
These exploratory subgroup analyses showed that sorafenib consistently improved median OS and DCR compared with placebo in patients with advanced HCC, irrespective of disease etiology, baseline tumor burden, performance status, tumor stage, and prior therapy.
Journal of Hepatology 06/2012; 57(4):821-9. · 9.86 Impact Factor
[show abstract][hide abstract] ABSTRACT: Systemic chemotherapy is the treatment of choice for inoperable (advanced or metastatic) cholangiocarcinoma. According to phase II and III trials, regimens combining 5-fluorouracil (5FU) or gemcitabine with a platinum salt have provided an overall response rate of 12-50% with a median overall survival of 5-16 months.
This was a retrospective analysis of 78 consecutive cases of inoperable cholangiocarcinoma treated by palliative chemotherapy from July 2005 to November 2009 in one center. We firstly aimed to evaluate the impact of palliative chemotherapy in terms of survival and secondly to analyze possible related prognostic factors.
This cohort included 25 female and 53 male patients, with a mean age of 60.8 ± 11.4 years. Intrahepatic and extrahepatic cholangiocarcinoma were observed in 57 and 21 patients, respectively. First-line chemotherapy regimens were as follows: gemcitabine (n = 7), gemcitabine plus oxaliplatin (with or without cetuximab; n = 62) and 5FU plus cisplatin (n = 9). None of the patients achieved a complete response. The partial response rate was 35.9% (27/78), and the stable disease rate was 26.9% (21/78), giving a disease control rate of 62.8%. At the time of this analysis, with a median follow-up of 18 months, 13 patients were survivors. Median overall survival was 10 months [95% confidence interval (CI) 7-12], and median progression-free survival was 7 months (95% CI 6-8). Upon univariate analysis, only the distribution of the disease was significantly linked with prognosis, with a median overall survival of 10 months (95% CI 10-24) for solitary tumors versus 7 months (95% CI 6-11) in the case of infiltrative or multifocal tumors (p = 0.039).
The disease control rate, overall survival and progression free-survival in this single-center retrospective study were in agreement with earlier reports. Specific features of this cohort were a large proportion of cholangiocarcinoma with associated cirrhosis (n = 30/78, 38.5%), mostly intrahepatic (n = 25/30, 83.5%). This confirms the increasing incidence of intrahepatic localization and the epidemiological link recently reported between intrahepatic biliary tract carcinoma and cirrhosis.
[show abstract][hide abstract] ABSTRACT: It has long been appreciated that hepatocellular carcinoma (HCC) is a complex disease. HCC is typically preceded by liver cirrhosis, which is itself caused by various types of hepatitis of both viral and nonviral etiologies. Thus, the treatment of patients with HCC requires multiple healthcare professionals, including hepatologists, medical oncologists, surgical oncologists, transplantation surgeons, diagnostic radiologists, pathologists, nurses, nurse practitioners and interventional radiologists. These specialists should meet regularly to review patients' progress, ensure that treatments are individualized for each patient and agree on next steps. We review case presentations provided by the authors to illustrate the benefits and advantages of the multidisciplinary team matrix in the management of patients with HCC, including the effects of this treatment technique on patient outcome, survival and quality of life.
Expert review of gastroenterology & hepatology 04/2012; 6(2):173-85.
[show abstract][hide abstract] ABSTRACT: Radioembolization of liver cancers using (90)Y-loaded microspheres is experiencing more widespread use. However, few data are available concerning the doses delivered to the tumors and the healthy liver. This retrospective study was conducted to calculate the tumor dosimetry (planned tumor dose [T(plan) D]) and nontumor dosimetry in patients treated by (90)Y-loaded glass microspheres and determine whether tumor dosimetry could predict response and survival.
Thirty-six patients with hepatocellular carcinoma (HCC), including 16 with portal vein thrombosis (PVT), were treated with (90)Y-loaded glass microspheres. The T(plan) D and the dose delivered to the injected healthy liver were calculated using a quantitative analysis of the (99m)Tc-macroaggregated albumin ((99m)Tc-MAA) SPECT/CT exam. Responses were assessed after 3 mo, using the criteria of the European Association for the Study of the Liver. Progression-free survival (PFS) and overall survival (OS) were evaluated using Kaplan-Meier tests.
The response rate was 69% for the overall population and 75% for the PVT patients. The dose delivered to the tumor was the only parameter associated with response with multivariate analysis (P = 0.019). A threshold T(plan) D value of 205 Gy was predictive of response, with a sensitivity of 100% and an accuracy of 91%. Quantitative (99m)Tc-MAA SPECT/CT allowed us to increase the injected activity for 4 patients with large lesions. PFS was only 5.2 mo and OS 9 mo when using a T(plan) D of less than 205 Gy versus 14 mo (P = 0.0003) and 18 mo (P = 0.0322), respectively, with a T(plan) D of 205 Gy or more.
Quantitative (99m)Tc-MAA SPECT/CT is predictive of response, PFS, and OS. Dosimetry based on (99m)Tc-MAA SPECT/CT can be used for the selection of patients and for an adaptation of treatment planning, especially in selected patients (particularly in the case of large tumors). These results also confirm the efficacy and safety of (90)Y-loaded microspheres in treating HCC, even in the presence of PVT (and especially when (99m)Tc-MAA uptake is seen inside the PVT).
Journal of Nuclear Medicine 02/2012; 53(2):255-63. · 5.77 Impact Factor
[show abstract][hide abstract] ABSTRACT: Hepatic markers are utilized in many classification systems of patients with hepatocellular carcinoma and, by measuring organ damage and tumor stage, can influence treatment. Moreover, elevated serum concentrations of aminotransferases and alpha-fetoprotein are indicators of poor prognosis in patients with hepatocellular carcinoma. We examined the effects of sorafenib on hepatic markers by performing exploratory subset analyses of the Sorafenib HCC Assessment Randomized Protocol (SHARP) trial in patients categorized by baseline concentrations of alanine aminotransferase/aspartate aminotransferase, alpha-fetoprotein, and bilirubin; and by evaluating the effects of sorafenib on bilirubin concentrations during treatment.
Patients (n=602) were grouped by baseline concentrations of alanine aminotransferase/aspartate aminotransferase (not significantly elevated, mildly elevated, or moderately elevated), alpha-fetoprotein (normal or elevated), and bilirubin (normal or elevated). Bilirubin was measured at baseline and on day 1 of each cycle.
Patients with elevated baseline concentrations of alanine aminotransferase/aspartate aminotransferase, alpha-fetoprotein, or bilirubin had shorter overall survival (OS) than those with normal baseline concentrations, irrespective of treatment group. No notable differences in safety profiles were observed between patients with normal vs. elevated alanine aminotransferase/aspartate aminotransferase, alpha-fetoprotein, or bilirubin. Median changes from baseline in bilirubin concentration at the last cycle of treatment were +0.17 and +0.19 mg/dl in the sorafenib and placebo groups, respectively.
These subset analyses suggest that sorafenib is safe and effective for hepatocellular carcinoma, irrespective of baseline alanine aminotransferase/aspartate aminotransferase, alpha-fetoprotein, or bilirubin concentration and that hepatic function remains stable over the course of sorafenib therapy.
Journal of Hepatology 01/2012; 56(5):1080-8. · 9.86 Impact Factor
[show abstract][hide abstract] ABSTRACT: Identifying gastroduodenal uptake of (99m)Tc-macroaggregated albumin (MAA), which is associated with an increased risk of ulcer disease, is a crucial part of the therapeutic management of patients undergoing radioembolization for liver tumours. Given this context, the use of MAA single photon emission computed tomography (SPECT)/CT may be essential, but the procedure has still not been thoroughly evaluated. The aim of this retrospective study was to determine the effectiveness of MAA SPECT/CT in identifying digestive extrahepatic uptake, while determining potential diagnostic pitfalls.
Overall, 139 MAA SPECT/CT scans were performed on 103 patients with different hepatic tumour types. Patients were followed up for at least 6 months according to standard requirements.
Digestive, or digestive-like, uptake other than free pertechnetate was identified in 5.7% of cases using planar imaging and in 36.6% of cases using SPECT/CT. Uptake sites identified by SPECT/CT included the gastroduodenal region (3.6%), gall bladder (12.2%), portal vein thrombosis (6.5%), hepatic artery (6.5%), coil embolization site (2.1%) as well as falciform artery (5.0%). For 2.1% of explorations, a coregistration error between SPECT and CT imaging could have led to a false diagnosis by erroneously attributing an uptake site to the stomach or gall bladder, when the uptake actually occurred in the liver.
SPECT/CT is more efficacious than planar imaging in identifying digestive extrahepatic uptake sites, with extrahepatic uptake observed in one third of scans using the former procedure. However, more than half of the uptake sites in our study were vascular in nature, without therapeutic implications. The risk of coregistration errors must also be kept in mind.
European Journal of Nuclear Medicine 01/2012; 39(5):872-80. · 4.53 Impact Factor
[show abstract][hide abstract] ABSTRACT: INTRODUCTION: The authors report two cases of young patients who developed clubbing and hypertrophic osteoarthropathy in one case or lung diffusion disorder in the second, after a long-term use of bevacizumab plus chemotherapy in a palliative setting of metastatic colorectal cancer. DISCUSSION: We propose that patients on long-term bevacizumab be examined for clubbing and undergo respiratory function tests and that this would be studied prospectively before beginning trials in evaluating this monoclonal antibody given for 2 years in an adjuvant setting.
Journal of Gastrointestinal Cancer 09/2011; 42(3):176-8.
[show abstract][hide abstract] ABSTRACT: A significant improvement in overall survival (OS) was demonstrated in patients with advanced hepatocellular carcinoma (HCC) who received sorafenib (Sor) in the Sorafenib HCC Assessment Randomized Protocol (SHARP) study, in contrast to a response rate (RR) of 2% assessed according to Response Evaluation Criteria in Solid Tumors (RECIST). Modified RECIST (mRECIST) were developed to assess the response in patients with HCC, based on measurement of viable tumor with arterial enhancement on a computed tomography (CT) scan. In the current study, mRECIST were evaluated and were compared with RECIST in patients who received Sor for advanced HCC.
The authors retrospectively analyzed 53 patients who received Sor for advanced HCC. Patients must to have undergone a 4-phase CT scan before treatment and repeatedly thereafter. CT scans were analyzed using RECIST 1.1 and mRECIST.
The rates of objective response (OR), stable disease (SD), and progressive disease (PD) were 2%, 79%, and 19%, respectively, according to RECIST and 23%, 57%, and 21%, respectively, according to mRECIST (P < .001). Patients who achieved an OR according to mRECIST had a longer OS than nonresponding patients with SD or PD (median OS, 18 months and 8 months, respectively; P = .013). In the 42 patients who achieved SD according to RECIST, OS differed depending on tumor response according to mRECIST, with a median OS of 17 months, 10 months, and 4 months for patients who achieved an OR (n = 11), SD (n = 29), and PD (n = 2), respectively (P = .016).
The current series validated mRECIST in patients who received Sor for advanced HCC. The majority of patients who had SD according to RECIST had a different prognosis according to mRECIST. The results indicated that, for patients with HCC, mRECIST should be used for the standard assessment of treatment efficacy, particularly in patients who are receiving antiangiogenic drugs.
Cancer 06/2011; 118(1):147-56. · 5.20 Impact Factor
[show abstract][hide abstract] ABSTRACT: To evaluate the characteristics of postoperative relapse, predictive factors and time to relapse after curative surgery for well-differentiated neuroendocrine tumours of the ileum, without hepatic or other distant metastases.
Clinical data of patients entered into the Groupe d'étude des Tumeurs Endocrines database were collected and analysed retrospectively to identify factors predictive of relapse.
Among 100 patients followed for a median of 56.5 (range 1-290) months, 42 relapsed after a median follow-up of 57.5 (range 6-176) months, with liver lesions in 27 (64.3%). Median disease-free survival (Kaplan-Meier) was 88 months (95% confidence interval 72-115). Disease-free survival was shorter for emergency surgery patients (p<0.01), patients with distant mesenteric lymph-node metastases (p<0.01), with fortuitous diagnosis (p=0.02), with tumour diameter >20mm (p=0.02), and those with multiple tumours (p=0.07). Multivariate analysis retained emergency surgery (odds-ratio 4.04 [95% confidence interval 2.01-8.11]), distant mesenteric lymph-node metastases (odds-ratio 2.53 [95% confidence interval 1.22-5.25]), and multiple tumours (odds-ratio 2.14 [95% confidence interval 1.01-4.50]), as being significantly associated with relapse.
Patients who underwent emergency surgery, with distant mesenteric lymph-node metastases or with multiple ileal tumours relapsed earlier. Closer monitoring for the patients with these risk factors may be required.
Digestive and Liver Disease 06/2011; 43(10):828-33. · 3.16 Impact Factor
[show abstract][hide abstract] ABSTRACT: The drug (131)I-labeled lipiodol is used as internal radiotherapy for unresectable hepatocellular carcinoma. Although the drug was considered safe during preapproval studies, we observed several cases of interstitial pneumonia following its administration.
Cases were retrospectively identified through the drug safety unit database of Rennes University Hospital.
From 1994 to 2009, interstitial pneumonia developed in 15 patients following (131)I-labeled lipiodol administration, with an estimated prevalence of 15.5 cases (95% CI, 7.7-23.2) per 1,000 treated patients. Mean age of the patients was 60 ± 8 years, and the male to female ratio was 6.5:1. All patients had cirrhosis, mainly related to long-term alcohol intoxication (n = 12). Most (n = 10) cases occurred after the second (131)I-labeled lipiodol injection. The median delay between last (131)I-labeled lipiodol administration and first respiratory symptoms was 30 days (interquartile range, 16.5-45 days). All patients presented with shortness of breath. Physical examination mostly revealed fever (n = 11) and bilateral crackles (n = 12). Chest CT scan showed bilateral ground-glass opacities (n = 8) with septal thickening, retraction, or both (n = 8). BAL (n = 7) was remarkable for increased neutrophils (n = 4) or CD8(+) T cell count (n = 3). Despite corticosteroids, 12 (80%) patients died, mostly of untractable respiratory failure (n = 9). Median delay between last (131)I-labeled lipiodol injection and death was 63 days (interquartile range, 34-129 days).
Interstitial pneumonia may be a serious and not uncommon complication of (131)I-labeled lipiodol administration.