[show abstract][hide abstract] ABSTRACT: PURPOSE: To evaluate the impact of dosimetry based on MAA SPECT/CT for the prediction of response, toxicity and survival, and for treatment planning in patients with hepatocellular carcinoma (HCC) treated with (90)Y-loaded glass microspheres (TheraSphere®). METHODS: TheraSphere® was administered to 71 patients with inoperable HCC. MAA SPECT/CT quantitative analysis was used for the calculation of the tumour dose (TD), healthy injected liver dose (HILD), and total injected liver dose. Response was evaluated at 3 months using EASL criteria. Time to progression (TTP) and overall survival (OS) were evaluated using the Kaplan-Meier method. Factors potentially associated with liver toxicity were combined to construct a liver toxicity score (LTS). RESULTS: The response rate was 78.8 %. Median TD were 342 Gy for responding lesions and 191 Gy for nonresponding lesions (p < 0.001). With a threshold TD of 205 Gy, MAA SPECT/CT predicted response with a sensitivity of 100 % and overall accuracy of 90 %. Based on TD and HILD, 17 patients underwent treatment intensification resulting in a good response rate (76.4 %), without increased grade III liver toxicity. The median TTP and OS were 5.5 months (2-9.5 months) and 11.5 months (2-31 months), respectively, in patients with TD <205 Gy and 13 months (10-16 months) and 23.2 months (17.5-28.5 months), respectively, in those with TD >205 Gy (p = 0.0015 and not significant). Among patients with portal vein thrombosis (PVT) (n = 33), the median TTP and OS were 4.5 months (2-7 months) and 5 months (2-8 months), respectively, in patients with TD <205 Gy and 10 months (6-15.2 months) and 21.5 months (12-28.5 months), respectively, in those with TD >205 Gy (p = 0.039 and 0.005). The median OS was 24.5 months (18-28.5 months) in PVT patients with TD >205 Gy and good PVT targeting on MAA SPECT/CT. The LTS was able to detect severe liver toxicity (n = 6) with a sensitivity of 83 % and overall accuracy of 97 %. CONCLUSION: Dosimetry based on MAA SPECT/CT was able to accurately predict response and survival in patients treated with glass microspheres. This method can be used to adapt the injected activity without increasing liver toxicity, thus defining a new concept of boosted selective internal radiation therapy (B-SIRT). This new concept and LTS enable fully personalized treatment planning with glass microspheres to be achieved.
European Journal of Nuclear Medicine 04/2013; · 4.53 Impact Factor
[show abstract][hide abstract] ABSTRACT: Portal vein tumor thrombosis (PVTT) is a common complication of hepatocellular carcinoma (HCC) and has a negative impact on prognosis. This characteristic feature led to the rationale of the present trial designed to assess the efficacy and the safety of yttrium-90 glass-microsphere treatment for advanced-stage lobar HCC with ipsilateral PVTT. 18 patients with unresectable lobar HCC and ipsilateral PVTT were treated in our institution with Y-microS radioembolization. Patients were evaluated every 3 to 6 months for response, survival, and toxicity. Mean follow-up was 13.0 months (2.2-50.6). Outcomes were: complete response ( = 2), partial response ( = 13), stable disease ( = 1), and progressive disease ( = 2) giving a disease control rate of 88.9%. Four patients were downstaged. Treating lobar hepatocellular carcinoma with ipsilateral portal vein thrombosis with yttrium-90 glass-microsphere radioembolization is safe and efficacious. Further clinical trials are warranted to confirm these results and to compare Y-microS with sorafenib, taking into account not only survival but also the possibility of secondary surgery for putative curative intention after downstaging.
International journal of hepatology. 01/2013; 2013:827649.
[show abstract][hide abstract] ABSTRACT: OBJECTIVE: To assess the impact of primary tumour resection on overall survival (OS) of patients diagnosed with stage IV colorectal cancer (CRC). DESIGN: Among the 294 patients with non-resectable colorectal metastases enrolled in the Fédération Francophone de Cancérologie Digestive (FFCD) 9601 phase III trial, which compared different first-line single-agent chemotherapy regimens, 216 patients (73%) presented with synchronous metastases at study entry and constituted the present study population. Potential baseline prognostic variables including prior primary tumour resection were assessed by univariate and multivariate Cox analyses. Progression-free survival (PFS) and OS curves were compared with the logrank test. RESULTS: Among the 216 patients with stage IV CRC (median follow-up, 33months), 156 patients (72%) had undergone resection of their primary tumour prior to study entry. The resection and non-resection groups did not differ for baseline characteristics except for primary tumour location (rectum, 14% versus 35%; p=0.0006). In multivariate analysis, resection of the primary was the strongest independent prognostic factor for PFS (hazard ratio (HR), 0.5; 95% confidence interval [CI], 0.4-0.8; p=0.0002) and OS (HR, 0.4; CI, 0.3-0.6; p<0.0001). Both median PFS (5.1 [4.6-5.6] versus 2.9 [2.2-4.1] months; p=0.001) and OS (16.3 [13.7-19.2] versus 9.6 [7.4-12.5]; p<0.0001) were significantly higher in the resection group. These differences in patient survival were maintained after exclusion of patients with rectal primary (n=43). CONCLUSION: Resection of the primary tumour may be associated with longer PFS and OS in patients with stage IV CRC starting first-line, single-agent chemotherapy.
European journal of cancer (Oxford, England: 1990) 08/2012; · 4.12 Impact Factor
[show abstract][hide abstract] ABSTRACT: La aparición de metástasis hepáticas resulta frecuente en el transcurso de la historia natural del cáncer (25%). Los principales tumores que causan metástasis hepáticas son los que drenan a través del sistema porta (50%), con el adenocarcinoma colorrectal en primer lugar (40%). Cuando constituyen la primera manifestación de la enfermedad, el problema diagnóstico no reside tanto en el carácter maligno de las lesiones como en su origen, ya que el pronóstico y el tratamiento son radicalmente distintos en función del tumor primario. En un primer momento, es preciso orientarse a partir de los datos clínicos y, si esto no es posible, hay que buscar con prioridad los cánceres sensibles a un tratamiento específico. Si el tumor primario no se identifica de manera sencilla, la biopsia de la lesión hepática es esencial para confirmar la naturaleza maligna de la lesión, determinar su tipo histológico y orientar hacia un tumor primario a través del estudio del fenotipo inmunohistoquímico tumoral. Con la excepción del cáncer colorrectal, los tumores de células germinales y el melanoma coroideo, cuyas metástasis hepáticas pueden ser objeto de resección quirúrgica, la orientación terapéutica en los demás tipos de cáncer es de tipo paliativo. Los recientes avances en su tratamiento oncológico han permitido mejorar su pronóstico, que, sin embargo, sigue siendo sombrío.
[show abstract][hide abstract] ABSTRACT: La comparsa di metastasi epatiche è frequente (25%) nel corso della storia naturale dei cancri. I principali tumori all’origine delle metastasi epatiche sono quelli che sono sottoposti a drenaggio attraverso il sistema portale (50%), con, in primo luogo, l’adenocarcinoma colorettale (40%). Quando sono rivelatrici, il problema diagnostico non è tanto quello della natura maligna delle lesioni quanto quello della loro origine, in quanto la prognosi e i trattamenti ipotizzati sono radicalmente diversi in funzione del cancro primitivo. Ci si orienta in un primo tempo in funzione dei dati clinici e, in mancanza di orientamento, si ricercano prioritariamente i cancri sensibili a un trattamento specifico. Se il cancro primitivo non è individuato semplicemente, la biopsia della lesione epatica è fondamentale per confermare la natura maligna della lesione, determinarne il tipo istologico e orientare verso un cancro primitivo grazie allo studio del fenotipo immunoistochimico tumorale. A eccezione del cancro colorettale, dei tumori germinali e del melanoma coroideo, cancri le cui metastasi epatiche possono essere resecate chirurgicamente, ci si orienta, per le altre neoplasie, verso un trattamento palliativo. I progressi recenti nella loro gestione oncologica hanno permesso di migliorare la loro prognosi, che rimane comunque infausta.
EMC - AKOS - Trattato di Medicina. 06/2012; 14(2):1–8.
[show abstract][hide abstract] ABSTRACT: This study is a retrospective analysis of 64 patients with a primary or secondary liver malignancy, referred for yttrium-90 radioembolisation between December 2006 and September 2010. Among these 64 patients, 54 received a total number of 69 injections (one to three treatments per patient). The mean activity injected per treatment was 3.1±1.6GBq. The liver targeted dose was 123.1±39Gy. Pulmonary shunt, detected in 55% of treatments, was 5.7%±7.4. The pulmonary dose was 4.7±7.1Gy. Overall, response rate per patient, evaluated at 3months by EASL or modified RECIST criteria, was 72.9%, 70% for hepatocellular carcinoma. The complication rate was relatively low (17%) with only two serious events. 90Y-microspheres radioembolisation of liver malignancies is an effective and well-tolerated therapy. Until now often used as a salvage therapy, the recent and ongoing studies should better define its place in the therapeutic strategy (adjuvant, neoadjuvant, first line) and possible association with chemotherapy and targeted therapies.
Medecine Nucleaire-imagerie Fonctionnelle Et Metabolique - MED NUCL. 01/2011; 35(4):224-231.
[show abstract][hide abstract] ABSTRACT: Hepatocellular carcinoma is now a major public health concern. In intermediate stages (one third of hepatocellular carcinoma patients), chemoembolization is the standard of care despite a poor tolerance and a moderate efficacy. Moreover, despite recent improvements, this technique seems in a dead end. Radioembolization could be an excellent tool for such patients. Currently 131I-Lipiodol, 188Re-Lipiodol, 90Y-glass or resin microspheres are available. More recent and promising data come from microspheres, but phase II and III studies are needed before drawing any conclusion. In the future, the combination of radioembolization with systemic chemotherapy or targeted agents (particularly antiangiogenic drugs) seems very promising.
Cancer Radiotherapie - CANCER RADIOTHER. 01/2011; 15(1):64-68.
[show abstract][hide abstract] ABSTRACT: Concurrent chemoradiotherapy is a valuable treatment option for localised oesophageal cancer (EC), but improvement is still needed. A randomised phase II trial was initiated to assess the feasibility and efficacy in terms of the endoscopic complete response rate (ECRR) of radiotherapy with oxaliplatin, leucovorin and fluorouracil (FOLFOX4) or cisplatin/fluorouracil.
Patients with unresectable EC (any T, any N, M0 or M1a), or medically unfit for surgery, were randomly assigned to receive either six cycles (three concomitant and three post-radiotherapy) of FOLFOX4 (arm A) or four cycles (two concomitant and two post-radiotherapy) of cisplatin/fluorouracil (arm B) along with radiotherapy 50 Gy in both arms. Responses were reviewed by independent experts.
A total of 97 patients were randomised (arm A/B, 53/44) and 95 were assessable. The majority had squamous cell carcinoma (82%; arm A/B, 42/38). Chemoradiotherapy was completed in 74 and 66%. The ECRR was 45 and 29% in arms A and B, respectively. Median times to progression were 15.2 and 9.2 months and the median overall survival was 22.7 and 15.1 months in arms A and B, respectively.
Chemoradiotherapy with FOLFOX4, a well-tolerated and convenient combination with promising efficacy, is now being tested in a phase III trial.
British Journal of Cancer 10/2010; 103(9):1349-55. · 5.08 Impact Factor
[show abstract][hide abstract] ABSTRACT: Patients with hepatocellular carcinoma (HCC) in a palliative setting have a poor prognosis despite recent therapeutic progress. Several prognostic scores, such as the BCLC and the CLIP, have been shown to be useful in helping select treatment options ranging from transplantation to palliative care. However, the discriminatory ability of these scores is inadequate in palliative settings, which concern about 70% of HCC patients. In this paper, we propose and validate a new prognostic score for patients in the palliative setting.
The prognostic score was developed on a set of 416 patients from a negative randomized clinical trial conducted by the Fédération Francophone de Cancers Digestifs. It was then subsequently validated on a second set of 271 patients from another negative trial. Backward selection was used to identify independent baseline characteristics. Measures of discrimination and predictive values were computed to assess the quality of the developed score. Comparisons with the BCLC and the CLIP - with and without the WHO performance status (PS) score - were performed.
Tumour morphology, portal vein obstruction, metastasis, ascites, jaundice, alpha-foetoprotein, and serum alkaline phosphatase were included in the final score. From the training dataset, three groups of increasing risk were defined, and these were associated with hazard ratios (HR) of 2.13 and HR = 5.72. Similar results were obtained on the validation dataset. This score provides a better discriminatory ability than BCLC and CLIP in this setting. Unfortunately, absolute performances for these scores remain poor.
The new prognostic score and CLIP + PS are recommended in palliative settings. However, new prognostic variables are necessary.
Journal of Hepatology 08/2010; 54(1):108-14. · 9.86 Impact Factor
[show abstract][hide abstract] ABSTRACT: The aim of this randomized multicenter phase III trial was to compare chemotherapy and interferon (IFN) in patients with metastatic carcinoid tumors. Patients with documented progressive, unresectable, metastatic carcinoid tumors were randomized between 5-fluorouracil plus streptozotocin (day 1-5) and recombinant IFN-alpha-2a (3 MU x 3 per week). Primary endpoint was progression-free survival (PFS). From February 1998 to June 2004, 64 patients were included. The two arms were well matched for median age, sex ratio, PS 0-1, previous chemotherapy, surgery, or radiotherapy. The median PFS for chemotherapy was 5.5 months versus 14.1 for IFN (hazard ratio=0.75 (0.41-1.36)). Overall survival (OS), tolerance, and effects on carcinoid symptoms were not significantly different. Despite a trend in favor of IFN, there was no difference in PFS and OS in advanced metastatic carcinoid tumors and therapeutic effect of both treatments was mild.
Endocrine Related Cancer 01/2009; 16(4):1351-1361. · 5.26 Impact Factor
[show abstract][hide abstract] ABSTRACT: The aims of our study were to assess quality of life (QoL) as a prognostic factor of overall survival (OS) and to determine whether QoL data improved three prognostic classifications among French patients with advanced hepatocellular carcinoma (HCC).
We pooled two randomized clinical trials conducted by the Fédération Francophone de Cancérologie Digestive in a palliative setting. In each trial QoL was assessed at baseline using the Spitzer QoL Index (0-10). Three prognostic classifications were calculated: Okuda, Cancer of the Liver Italian Program (CLIP), and Barcelona Clinic Liver Cancer group (BCLC) scores. To explore whether the scores could be improved by including QoL, univariate Cox analyses of all potential baseline predictors were performed. A final multivariate Cox model was constructed including only significant multivariate baseline variables likely to result in improvement of each scoring system. In order to retain the best prognostic variable to add for each score, we compared Akaike information criterion, likelihood ratio, and Harrell's C-index. Cox analyses were stratified for each trial.
Among 538 included patients, QoL at baseline was available for 489 patients (90%). Longer median OS was significantly associated with higher Spitzer scores at baseline, ranging from 2.17 months (Spitzer=3) to 8.93 months (Spitzer=10). Variables retained in the multivariate Cox model were: jaundice, hepatomegaly, hepatalgia, portal thrombosis, alphafetoprotein, bilirubin, albumin, small HCC, and Spitzer QoL Index (hazard ratio=0.84 95% CI [0.79-0.90]). According to Harrell's C-index, QoL was the best prognostic variable to add. CLIP plus the Spitzer QoL Index had the most discriminating value (C=0.71).
Our results suggest that QoL is an independent prognostic factor for survival in HCC patients with mainly alcoholic cirrhosis. The prognostic value of CLIP score could be improved by adding Spitzer QOL Index scores.
Quality of Life Research 08/2008; 17(6):831-43. · 2.41 Impact Factor
[show abstract][hide abstract] ABSTRACT: The objective of this study was to assess the performance of three staging systems [Okuda, Cancer of the Liver Italian Program (CLIP) and Barcelona Clinic Liver Cancer group (BCLC)], for predicting survival in patients with hepatocellular carcinoma (HCC) and to explore how to improve prognostic classification among French patients with HCC whose main etiology is alcoholic cirrhosis.
We have pooled two randomized clinical trials in palliative condition from the Fédération Francophone de Cancerologie Digestive. They had included 416 and 122 patients. Performances of Okuda, CLIP and BCLC scores have been compared using Akaike information criterion, discriminatory ability (Harrell's C and the Royston's D statistics), monotonicity of gradients and predictive accuracy (Schemper statistics Vs). To explore how to improve classifications, univariate and multivariate Cox model analyses were carried out.
The pooled database included 538 patients. The median survival was 5.3 months (95% confidence interval 4.6-6.2). For all statistics CLIP staging system had a better prognostic ability. Performances of all staging systems were rather disappointing. World Health Organization performance status (WHO PS) for CLIP or alpha-fetoprotein for BCLC allowed a significant improvement of prognostic information.
Our results indicate that CLIP staging seems to be most adapted to palliative setting and that it could be better by associating WHO PS.
Annals of Oncology 07/2008; 19(6):1117-26. · 7.38 Impact Factor