[Show abstract][Hide abstract] ABSTRACT: Background:
To determine efficacy and toxicity of radiation therapy combined with oxaliplatin, 5-fluorouracil, and folinic acid (FOLFOX) and cetuximab in patients with locally advanced oesophageal cancer.
Patients and methods:
Patients with stage III oesophageal or gastro-oesophageal junction cancer were enrolled in a Simon's two-stage phase II study. Patients received FOLFOX and weekly cetuximab on week 1-10 with concurrent radiotherapy (50.4 Gy in 30 fractions) on week 5-10. Primary end-point was clinical overall response rate (ORR). An ORR rate of more than 50% was expected.
Among the 79 included patients, clinical ORR was 77% with 40% complete responses. Median overall survival and progression-free survival were 21.6 and 11.3 months, respectively. The most common grade III-IV toxicities observed during experimental chemoimmunotherapy followed by chemoradiation included neutropenia (28%), oesophagitis (12%), rash (11%), and allergy (9%). There was one treatment-related death due to oesophagitis with gastrointestinal bleeding.
Cetuximab-FOLFOX regimen combined with radiotherapy demonstrated its efficacy and was well tolerated. Unfortunately, these results were not confirmed in two recent phase III studies.
Full-text · Article · Mar 2016 · European journal of cancer (Oxford, England: 1990)
[Show abstract][Hide abstract] ABSTRACT: Objective:
To assess the prognostic value of clinical and biological features in patients treated with second-line targeted therapies (TT) for a metastatic renal cell carcinoma (mRCC).
Material and methods:
A retrospective study was performed including 60patients treated with second-line TT from 2006 to 2013. Clinical and biological features were collected, including TT-induced toxicities, Heng and MSKCC prognostic scores, and renal function. Overall survival (OS) and progression-free survival (PFS) were assessed using univariate and multivariate analysis.
The median age was 61years [39-81]. MSKCC and Heng scores were significantly prognostic for OS and PFS (P<0.05). Hypo-albuminemia, anemia and brain metastasis were associated with poorer OS and PFS (P<0.05). Severe induced toxicities had a prognostic impact with higher OS (26months vs 10months, P=0.003) and PFS (5months vs 4months, P=0.047). Renal function impairment at the initiation of the second line was also associated with higher survival (OS=24months vs 9months, P=0.035 and PFS=7months vs 4months, P=0.043). On multivariate analysis, induced toxicity was found as an independent factor of good prognosis for OS (HR=0.36; P=0.01).
Our results suggested that renal function impairment and TT-induced toxicities in the second line of treatment for mRCC have a potential prognostic interest as it had previously been reported for the first line of TT.
Level of evidence:
No preview · Article · Oct 2015 · Progrès en Urologie
[Show abstract][Hide abstract] ABSTRACT: Purpose:
Although considered safer than central venous catheters for administration of cancer chemotherapy, totally implanted venous access (TIVA) is associated with adverse events that may impair prognosis and quality of life of patients receiving chemotherapy. Our aim was to assess the feasibility and interest of surveillance of cancer chemotherapy TIVA-adverse events (AE), associated with morbidity-mortality conferences (MMCs) on TIVA-AE.
We performed a prospective interventional study in two hospitals (a university hospital and a comprehensive care center). For each cancer chemotherapy care pathway within each hospital, we set up surveillance of TIVA-AE and MMC on these events. Patients included in surveillance were those with a TIVA either placed or used for chemotherapy cycles in one of the participating wards. Feasibility of MMC was assessed by the number of MMC meetings that actually took place and the number of participants at each meeting. The interest of MMC was assessed by the number of TIVA-AE identified and analyzed, and the number and type of improvement actions selected and actually implemented.
We recorded 0.41 adverse events per 1000 TIVA-day. MMCs were implemented in all care pathways, with sustained pluriprofessional attendance throughout the survey; 39 improvement actions were identified during meetings, and 18 were actually implemented.
Surveillance of TIVA-AE associated with MMC is feasible and helps change practices. It could be useful for improving care of patients undergoing cancer chemotherapy.
No preview · Article · Oct 2015 · Supportive Care in Cancer
[Show abstract][Hide abstract] ABSTRACT: To assess the impact of baseline chronic kidney disease on targeted therapy (TT)-induced toxicities and survival in patients treated for metastatic renal cell carcinoma (mRCC). Data from patients receiving first-line TT from January 2006 to June 2012 were collected retrospectively. TT side effects, time to treatment failure (TTF), and overall survival (OS) were analyzed according to the baseline glomerular filtration rate (GFR) calculated using the modification diet in renal disease formula. Hundred and two patients treated with sunitinib (N=67), sorafenib (N=24), or temsirolimus (N=11) were included. Forty-two patients (41%) had baseline chronic kidney disease with GFR less than 60 ml/min/1.73 m. Patients with GFR less than 60 were more likely to encounter severe (grade 3-4) TT-induced toxicities (79 vs. 32%, P<0.0001). Moreover, renal function impairment was significantly associated with higher median TTF and OS (respectively, 12 vs. 6 months for TTF, P=0.003; and 33 vs. 13 months for OS, P=0.001). On multivariate analysis, GFR less than 60 was identified as the only factor associated with a higher rate of severe toxicity: odds ratio=4.74 (1.67-13.41), P=0.003. Severe toxicity (P=0.05) was identified as an independent prognostic factor for OS and TTF. Baseline chronic kidney disease was associated with higher TT-induced toxicities, which were identified as a prognostic factor of higher survival in mRCC treatment. These results suggest that GFR measurement could be used to optimize the efficacy of TT in patients treated for an mRCC.
No preview · Article · May 2015 · Anti-cancer drugs
[Show abstract][Hide abstract] ABSTRACT: The high failure rates in the radiotherapy (RT) target volume suggest that patients with locally advanced oesophageal cancer (LAOC) would benefit from increased total RT doses. High 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) uptake (hotspot) on pre-RT FDG positron emission tomography (PET)/CT has been reported to identify intra-tumour sites at increased risk of relapse after RT in non-small cell lung cancer and in rectal cancer. Our aim was to confirm these observations in patients with LAOC and to determine the optimal maximum standardized uptake value (SUVmax) threshold to delineate smaller RT target volumes that would facilitate RT dose escalation without impaired tolerance.
The study included 98 consecutive patients with LAOC treated by chemoradiotherapy (CRT). All patients underwent FDG PET/CT at initial staging and during systematic follow-up in a single institution. FDG PET/CT acquisitions were coregistered on the initial CT scan. Various subvolumes within the initial tumour (30, 40, 50, 60, 70, 80 and 90 % SUVmax thresholds) and in the subsequent local recurrence (LR, 40 and 90 % SUVmax thresholds) were pasted on the initial CT scan and compared[Dice, Jaccard, overlap fraction (OF), common volume/baseline volume, common volume/recurrent volume].
Thirty-five patients had LR. The initial metabolic tumour volume was significantly higher in LR tumours than in the locally controlled tumours (mean 25.4 vs 14.2 cc; p = 0.002). The subvolumes delineated on initial PET/CT with a 30-60 % SUVmax threshold were in good agreement with the recurrent volume at 40 % SUVmax (OF = 0.60-0.80). The subvolumes delineated on initial PET/CT with a 30-60 % SUVmax threshold were in good to excellent agreement with the core volume (90 % SUVmax) of the relapse (common volume/recurrent volume and OF indices 0.61-0.89).
High FDG uptake on pretreatment PET/CT identifies tumour subvolumes that are at greater risk of recurrence after CRT in patients with LAOC. We propose a 60 % SUVmax threshold to delineate high FDG uptake areas on initial PET/CT as reduced target volumes for RT dose escalation.
Full-text · Article · Feb 2015 · European journal of nuclear medicine and molecular imaging
[Show abstract][Hide abstract] ABSTRACT: Purpose:
It has been suggested that FDG PET has predictive value for the prognosis of treated oesophageal carcinoma. However, the studies reported in the literature have shown discordant results. The aim of this study was to determine whether pretherapy quantitative metabolic parameters correlate with patient outcomes.
Included in the study were 67 patients with a histological diagnosis of oesophageal squamous cell carcinoma. Each patient underwent (18)F-FDG PET (4.5 MBq/kg) before chemoradiotherapy. Quantitative analysis was performed using the following parameters: age, weight loss, location, N stage, OMS performance status, MTVp and MTVp' (metabolic tumour volume determined by two different physicians), MTV40% (volume for a threshold of 40 % of SUVmax), MTVa (volume automatically determined with a contrast-based adaptive threshold method), SUVmax, SUVmean and TLG (total lesion glycolysis).
MTVp and MTV40% were highly correlated (Pearson's index 0.92). SUVmeanp and SUVmean40% were also correlated (Pearson's index 0.86), as were TLGp and TLG40% (Pearson's index 0.98). Similarly, the parameters obtained with the adaptive threshold method (MTVa, SUVmeana and TLGa) were correlated with those obtained manually (MTVp, SUVmeanp and TLGp). The manual metabolic tumour volume determination (MTVp and MTVp') was reproducible. Multivariate analysis for disease-free survival (DFS) showed that a larger MTVp was associated with a shorter DFS (p = 0.004) and that a higher SUVmax was associated with a longer DFS (p = 0.02). Multivariate analysis for overall survival (OS) showed that a larger MTVp was associated with a shorter OS (p = 0.01) and that a tumour in the distal oesophagus was associated with a longer OS (p = 0.005). The associations among the other parameters were not statistically significant.
Metabolic tumour volume is a major prognostic factor for DFS and OS in patients with oesophageal squamous cell carcinoma. Higher SUVmax values were paradoxically associated with longer survival. The location of the tumour also appeared to affect prognosis.
No preview · Article · Jul 2014 · European journal of nuclear medicine and molecular imaging
[Show abstract][Hide abstract] ABSTRACT: Objective
To assess the prognostic value of clinical and biological variables in the era of targeted therapies, especially induced toxicity in patients treated for metastatic renal cell carcinoma (RCC).
Patients and methods
A retrospective single-center study was performed in patients treated in our center from 2006 to 2012. The clinical and biological variables and toxicity data were retrospectively collected. Survival rates were calculated using the Kaplan-Meier method and compared by the Log-Rank test. Multivariate analysis was also performed using the Cox model.
One hundred and two patients were included, with a median follow-up of 20 months. The median overall survival (OS) was 21 months, and 6 months for the progression free survival (PFS). As expected, the variables included in the Mozter prognostic score had a significant impact on OS (P < 0.0001) and PFS (P < 0.0001). However, hypoalbuminemia (P < 0.0001), brain metastasis (P = 0.003) and the absence of nephrectomy (P < 0.0001) were found as poor prognosis factors for OS. In addition, severe toxicity (grade 3-4) was significantly associated with higher OS (P < 0.0001) and PFS (P = 0.0003) and appeared as an independent factor in multivariate analysis for OS (P = 0.02) and PFS (P = 0.01).
Severe toxicity induced by targeted therapies was found as a prognostic factor increasing significantly the survival. Further studies are needed to assess the real value of this factor in the development of sequential therapies for the treatment of RCC.
No preview · Article · Jul 2014 · Progrès en Urologie
[Show abstract][Hide abstract] ABSTRACT: The objective of this study is to investigate the feasibility and the additional interest of a parametric imaging (PI) method to monitor the early tumour metabolic response in a prospective series of oesophageal cancer patients who underwent positron emission tomography with fluoro-2-deoxy-d-glucose (FDG-PET/CT) before and during curative-intent chemo-radiotherapy.
Fifty-seven patients with squamous cell carcinoma (SCC) of the oesophagus prospectively underwent FDG-PET/CT before chemo-radiotherapy (CRT) (PET1) and at 21 +/- 3 days after the beginning of CRT (PET2). The outcome was assessed at 3 months and 1 year after the completion of CRT (clinical examination, CT scan or FDG-PET/CT, biopsy). For each patient, PET1 and PET2 were registered using CT images. The 2 PET image sets were subtracted, so the voxels with significant changes in FDG uptake were identified. A model-based analysis of this graph was used to identify the tumour voxels in which significant changes occurred between the two scans and yielded indices characterising these changes (green and red clusters). Quantitative parameters were compared with clinical outcome at 3 months and at 1 year.
The baseline tumour FDG uptake decreased significantly at PET2 (p < 0.0001). The tumour volume significantly decreased between PET1 and PET2 (p < 0.02). The initial functional volume of the lesion (TV1) was significantly lower (p < 0.02) in patients in clinical response (CR) at 3 months and 1 year. The volume of the lesion during the treatment (TV2) was significantly lower in patients identified as in CR at 3 months (p < 0.03), but did not predict the outcome at 1 year. Multivariate analyses of outcome at 3 months showed that the risk of failure/death increased with younger age (p = 0.001), larger metabolic volume on PET1 (p = 0.009) and larger volume with decreased FDG uptake (p = 0.047). As for outcome at 1 year, the risk of failure/death increased with younger age (p = 0.006), nodal involvement (p = 0.08) and larger volumes with increased uptake (p = 0.03).
A parametric method to assess tumour response on serial FDG-PET performed during chemo-radiotherapy was evaluated. Early metabolic changes, i.e. variations in FDG uptake, provided additional prognostic information in multivariate analyses ClinicalTrials.gov NCT 00934505.Trial registration: Current Controlled Trials ISRCTN7824458.
[Show abstract][Hide abstract] ABSTRACT: Undernutrition is frequently observed in patients with a locally advanced oesophageal carcinoma. However, variations of nutritional parameters during chemoradiotherapy have not been thoroughly investigated.
To evaluate the characteristics and the impact of nutritional variations during treatment.
Weight loss, body mass index (BMI), serum albumin level and daily food intake at baseline and during treatment (T1=week 1; T2=week 5 or 8; T3=week 11) were retrospectively analyzed in 101 patients with oesophageal carcinoma.
Significant variations occurred during chemoradiotherapy with a decrease in serum albumin level (p<0.001), body mass index (p<0.001) and weight (p<0.001). Response rate to treatment was significantly lower in patients with undernutrition at T1 (p=0.05), from T1 to T2 (p=0.01) and from T1 to T3 (p=0.04). Median overall survival was 25 months in patients with persistent undernutrition from T1 to T2 vs 42 months in wellnourished patients from T1 to T2 and those malnourished only at T1 or T2 (p=0.05). In responders, patients presenting with a lower weight or a lower food intake from T1 to T3 had worse survival (33 vs 59 months, p<0.001 and 29 vs 61 months, p=0.001, respectively).
Significant variations of nutritional parameters occurred during chemoradiotherapy with a worse impact on response and survival.
No preview · Article · Jan 2014 · Digestive and Liver Disease
[Show abstract][Hide abstract] ABSTRACT: Background:
Small bowel adenocarcinoma (SBA) is a rare tumour with a poor prognosis. Molecular biology data on SBA carcinogenesis are lacking.
Expression of HER2, β-catenin, p53 and mismatch repair (MMR) protein was assessed by immunohistochemistry. KRAS, V600E BRAF mutations and microsatellite instability were investigated.
We obtained samples from 63 SBA patients (tumour stages: I–II: 30% III: 35% IV: 32% locally advanced: 3%). HER2 overexpression (3+) was observed in 2 out of 62 patients, overexpression of p53 in 26 out of 62, abnormal expression of β-catenin in 12 out of 61, KRAS mutation in 21 out of 49, BRAF V600E mutation in 1 out of 40 patients, MMR deficiency (dMMR) in 14 out of 61 and was consistent with Lynch syndrome in 9 out of 14 patients. All of the dMMR tumours were in the duodenum or jejunum and only one was stage IV. Median overall survival (OS) was 36.6 months (95% CI, 26.9–72.2). For all patients, in univariate analysis, stages I–II (P<0.001), WHO PS 0–1 (P=0.01) and dMMR phenotype (P=0.02) were significantly associated with longer OS. In multivariate analysis, disease stage (P=0.01) and WHO PS 0–1 (P=0.001) independently predicted longer OS. For stage IV patients, median OS was 20.5 months (95% CI: 14.6; 36.6 months). In multivariate analysis, WHO PS 0–1 (P=0.0001) and mutated KRAS status (P=0.02) independently predicted longer OS.
This large study suggests that molecular alterations in SBA are closer to those in colorectal cancer (CRC) than those in gastric cancer, with low levels of HER 2 overexpression and high frequencies of KRAS mutations. The seemingly higher frequency of dMMR than in CRC may be explained by the higher frequency of Lynch syndrome in SBA patients. A dMMR phenotype was significantly associated with a non-metastatic tumour (P=0.02). A trend for a good prognosis and a duodenum or jejunum primary site was associated with dMMR.
Full-text · Article · Nov 2013 · British Journal of Cancer