Is Chemoembolisation of Value in Inoperable Primary Hepatocellular Carcinoma

primary treatment for unresectable hepatocellular carcinoma (HCC). In this unit, 185 patients with a new diagnosis of HCC not amenable to surgery were seen between 1988 and 1991. Intended therapy for these patients was chemoembolisation with doxorubicin (60 mg/m2) and lipiodol, repeated at six week intervals until it was technically no longer possible o.r until complete tumour response had been obtained. Chemoembolisation was possible in 67 of the 185 (37%). Reasons for exclusion were portal vein occlusion (n=36), decompensated cirrhosis (n 44), distant metastases (n=5), diffuse tumour or unsuitable anatomy (tumour or vasculature) (n=11), patient refusal (n=11), and other (n=11). Patients excluded from treatment survived for a median of 10 weeks (range 3 days-19 months). In patients treated, 18 had small HCC (4cm) and 49 had large or multifocal HCC. Chemoembolisation was carried out a median of two sessions for small and three sessions for large tumours. Ten of 18 patients with small HCC showed a 50% or greater reduction in tumour size. Five of 49 patients with large or multifocal tumours showed a response to treatment. Median overall survival for treated patients was 36 weeks (range 3 days–4 years). One patient has subsequently undergone liver transplantation with no recurrence and minimal residual disease at transplantation. Two other patients are alive three years after chemoembolisation, one with no evidence of recurrent disease. No patient was thought suitable for surgery after their response to chemoembolisation. Chemotherapy related complications were seen in 22%. Complications were significantly more common in patients with larger tumours and poor liver reserve. Five patients died as a result of chemotherapy related complications. In conclusion, only one third of UK patients with unresectable HCC are treatable by chemoembolisation. Results with small tumours are encouraging, with a high response rate and the possibility of surgical intervention in previously inoperable disease. Large tumours, however, show a poor response and significant incidence of side effects, suggesting that this treatment offers little benefit in advanced disease

Terrestrial and fluvial carbon fluxes in a tropical watershed: Nyong basin, Cameroon

The Nyong watershed, with an area of 27 800 km2 and a mean annual discharge of 390 m3 s−1, is the second largest river in Cameroon. The Nyong watershed serves as an outstanding study area for the examination of carbon fluxes in humid tropical environments because of its limited anthropogenic impact and homogeneous silicate bedrock. Between April 2005 and April 2007, we sampled water at seven stations, from the small watershed of the Mengong (0.6 km2) to the Nyong at Edea (24 500 km2), and monitored temperature, pH, dissolved inorganic carbon (DIC) and dissolved organic carbon (DOC) contents, as well as the isotopic composition of DIC (δ13CDIC)andDOC(δ13CDOC).We estimated terrestrial net ecosystemproductivity in theNyong River watershed and measured fluvial fluxes of carbon to the ocean and the atmosphere. The Nyong River basin sequesters significant amounts of carbon on an annual basis: ~7 920 000t C year−1 (300 g C m−2 year−1). The combined dissolved organic, dissolved inorganic and atmospheric fluxes of carbon from the Nyong River only export 3% of this flux fromthe basin on an annual basis. This includes a minimumCO2 outgassing of 1487 g Cm−2 year−1, comparable to 115% of the annual flux of DOC and four times greater than the flux of DIC

Cetuximab in combination with irinotecan/5-fluorouracil/folinic acid (FOLFIRI) in the initial treatment of metastatic colorectal cancer: a multicentre two-part phase I/II study

This study was designed to investigate the efficacy and safety of the epidermal growth factor receptor (EGFR) inhibitor cetuximab combined with irinotecan, folinic acid (FA) and two different doses of infusional 5-fluorouracil (5-FU) in the first-line treatment of EGFR-detectable metastatic colorectal cancer.Clinical Trial, Phase IClinical Trial, Phase IIJournal ArticleMulticenter StudyResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

Management of Esophageal Carcinoma Associated with Cirrhosis: A Retrospective Case-Control Analysis

Objectives. Esophageal carcinoma and cirrhosis have the overlapping etiologic factors. Methods. In a retrospective analysis conducted in 2 Breton institutions we wanted to asses the frequency of this association and the outcome of these patients in a case-control study where each case (cirrhosis and esophageal cancer) was paired with two controls (esophageal cancer). Results. In a 10-year period, we have treated 958 esophageal cancer patients; 26 (2.7%) had a cirrhosis. The same treatments were proposed to the 2 groups; cases received nonsignificantly different radiation and chemotherapy dose than controls. Severe toxicities and deaths were more frequent among the cases. At the end of the treatment 58% of the cases and 67% of the controls were in complete remission; median and 2-year survival were not different between the 2 groups. All 4 Child-Pugh B class patients experienced severe side effects and 2 died during the treatment. Conclusions. This association is surprisingly infrequent in our population! Child-Pugh B patients had a dismal prognosis and a bad tolerance to radiochemotherapy; Child-Pugh A patients have the same tolerance and the same prognosis as controls and the evidence of a well-compensated cirrhosis has not modified our medical options

Impact of radiotherapy in the management of locally advanced extrahepatic cholangiocarcinoma

BACKGROUND: Optimal therapy for patients with unresectable locally advanced extrahepatic cholangiocarcinoma (ULAC) remains controversial. We analysed the role of radiotherapy in the management of such tumors. METHODS: We retrospectively reviewed the charts of patients treated in our institution with conformal-3D external-beam-radiotherapy (EBRT) with or without concurrent chemotherapy. RESULTS: Thirty patients were included: 24 with a primary tumor (group 1) and 6 with a local relapse (group 2). Toxicity was low. Among 25 patients assessable for EBRT response, we observed 9 complete responses, 4 partial responses, 10 stabilisations, and 2 progressions. The median follow-up was 12 months. Twenty out of 30 patients (66%) experienced a relapse, which was metastatic in 75% of cases in the whole series, 87% in group 1, 60% in group 2 (p = 0.25). Twenty-eight patients (93%) died of relapse or disease complications. Median overall survivals in the whole group and in group 1 or 2 were respectively 12, 11 and 21 months (p = 0.11). The 1-year and 3-year progression-free survivals were respectively 38% and 16% in the whole series; 31% and 11% in group 1, 67% and 33% in group 2 (p = 0.35). CONCLUSION: EBRT seems efficient to treat ULAC, with acceptable toxicity. For primary disease, the high rate of metastatic relapse suggests to limit EBRT to non-progressive patients after induction chemotherapy

Modalities and indications of locoregional treatments in digestive neuroendocrine tumours

Les traitements locorégionaux des métastases hépatiques des tumeurs neuroendocrines du tube digestif sont dominés par la chimioembolisation et la radioembolisation. La chimioembolisation (usuellement à la doxorubicine ou à la streptozotocine) est bien tolérée et efficace sur les symptômes notamment sécrétoires et sur la taille tumorale (taux de réponse objective entre 30 et 60 %) ; son bénéfice en survie est très probable. L’utilisation des billes chargées en chimiothérapie semble prometteuse mais sa tolérance est mal évaluée. La radioembolisation aux microsphères chargées à l’Yttrium 90 semble également efficace et bien tolérée. Les contre-indications (notamment les anastomoses biliodigestives) doivent être connues pour limiter les toxicités. Les indications ne sont pas bien codifiées mais ces traitements semblent raisonnables dans les maladies métastatiques classées G1 ou G2 évolutives en première (carcinoïdes) ou seconde/troisième ligne (tumeurs pancréatiques) thérapeutique.Loco-regional treatments of liver metastases from neuroendocrine tumors are represented by transarterial chemoembolization (TACE) and radioembolization. TACE (usually with doxorubicin or streptozotocin) is well tolerated and associated with symptomatic improvements and objective tumor responses rates ranging from 30 to 60%. The use of chemotherapy-loaded microspheres seems promising. Radioembolization (90Y-microspheres) also gives promising results. Contra-indications, particularly bilio-digestive anastomosis, need to be considered in order to avoid severe side effects. Best indications are not well recognized, but progressive metastases from G1-G2 tumors in first (GI tract) or second/third (pancreatic tumors) lines seem to benefit from those therapeutic options

Utility of Quantitative 99mTc-MAA SPECT/CT for 90yttrium-Labelled Microsphere Treatment Planning: Calculating Vascularized Hepatic Volume and Dosimetric Approach

Objectives. The aim of this study was to assess the effectiveness of SPECT/CT for volume measurements and to report a case illustrating the major impact of SPECT/CT in calculating the vascularized liver volume and dosimetry prior to injecting radiolabelled yttrium-90 microspheres (Therasphere). Materials and Methods. This was a phantom study, involving volume measurements carried out by two operators using SPECT and SPECT/CT images. The percentage of error for each method was calculated, and interobserver reproducibility was evaluated. A treatment using Therasphere was planned in a patient with three hepatic arteries, and the quantitative analysis of SPECT/CT for this patient is provided. Results. SPECT/CT volume measurements proved to be accurate (mean error <6% for volumes ≥16 cm3) and reproductive (interobserver agreement = 0.9). In the case report, 99mTc-MAA SPECT/CT identified a large liver volume, not previously identified with angiography, which was shown to be vascularized after selective MAA injection into an arterial branch, resulting in a large modification in the activity of Therasphere used. Conclusions. MAA SPECT/CT is accurate for vascularized liver volume measurements, providing a valuable contribution to the therapeutic planning of patients with complex hepatic vascularization

Determination of an optimal response cut-off able to predict progression-free survival in patients with well-differentiated advanced pancreatic neuroendocrine tumours treated with sunitinib: an alternative to the current RECIST-defined response.

BACKGROUND: Sunitinib prolongs progression-free survival (PFS) in patients with advanced pancreatic neuroendocrine tumours (pNET). Response Evaluation Criteria in Solid Tumors (RECIST)-defined partial responses (PR; classically defined as ⩾30% size decrease from baseline) are infrequent. METHODS: Individual data of pNET patients from the phase II [NCT00056693] and pivotal phase III [NCT00428597] trials of sunitinib were analysed in this investigator-initiated, post hoc study. The primary objective was to determine the optimal RECIST (v.1.0) response cut-off value to identify patients who were progression-free at 11 months (median PFS in phase III trial); and the most informative time-point (highest area under the curve (AUC) by receiver operating characteristic (ROC) analysis and logistic regression) for prediction of benefit (PFS) from sunitinib. RESULTS: Data for 237 patients (85 placebo; 152 sunitinib (n=66.50 mg \u274-weeks on/2-weeks off\u27 schedule; n=86 \u2737.5 mg continuous daily dosing (CDD)\u27)) and 788 scans were analysed. The median PFS for sunitinib and placebo were 9.3 months (95% CI 7.6-12.2) and 5.4 months (95% CI 3.5-6.01), respectively (hazard ratio (HR) 0.43 (95% CI 0.29-0.62); P CONCLUSIONS: A 10% reduction within marker lesions identifies pNET patients benefiting from sunitinib treatment with implications for maintenance of dose intensity and future trial design

Objective response by mRECIST as a predictor and potential surrogate end point of overall survival in advanced HCC

Background & Aims: The Modified Response Evaluation Criteria in Solid Tumors (mRECIST) was developed to overcome the limitations of standard RECIST criteria in response assessment of hepatocellular carcinoma (HCC). We aimed to investigate whether objective response by mRECIST accurately predicted overall survival (OS) in patients with advanced HCC treated with systemic targeted therapies and also to preliminarily assess this endpoint as a potential surrogate of OS.Methods: Individual patient data from the BRISK-PS randomized phase III trial comparing brivanib vs. placebo (the first to prospectively incorporate mRECIST) were used to analyze objective response as a predictor of OS in a time-dependent covariate analysis. Patients with available imaging scans during follow-up were included (n = 334; 85% of those randomized). Moreover, a correlation of the survival probability in deciles vs. the observed objective response was performed to evaluate its suitability as a surrogate end-point.Results: Objective response was observed in 11.5% and 1.9% of patients treated with brivanib and placebo respectively, and was associated with a better survival (median OS 15.0 vs. 9.4 months, p < 0.001). In addition, objective response had an independent prognostic value (HR = 0.48; 95% confidence interval [CI], 0.26-0.91, p = 0.025) along with known prognostic factors. Finally, objective response showed promising results as a surrogate of OS in this trial (R = -0.92; 95% CI, -1 to -0.73, p < 0.001). It was an early indicator of the treatment effect (median time to objective response was 1.4 months).Conclusions: Objective response by mRECIST in advanced HCC predicts OS and thus can be considered as a candidate surrogate end-point. Further studies are needed to support this finding.Lay summary: There is a need to identify surrogate end-points for overall survival in advanced hepatocellular carcinoma. We studied patients from the phase III BRISK trial, comparing brivanib treatment with placebo after sorafenib progression. We demonstrate that objective response is an independent predictor of survival and qualifies as a potential surrogate end-point for overall survival in this patient population.Clinical trial number: NCT00825955